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A History of Ultraviolet Photobiology for Humans, Animals and Microorganisms¶

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A History of Ultraviolet Photobiology for Humans, Animals and Microorganisms¶

Photochemistry and Photobiology, 2002, 76(6): 561–579
Invited Review
A History of Ultraviolet Photobiology for Humans,
Animals and Microorganisms
{
Philip E. Hockberger*
Department of Physiology, The Feinberg School of Medicine, Northwestern University, Chicago, IL
Received 12 June 2002; accepted 20 September 2002
INTRODUCTION
Ancient civilizations understood that sunlight provides visibility,
warmth, health and vitality. Their understanding of how sunlight
provides these life-sustaining influences was immersed in mythol-
ogy and cultural traditions. Offspring, dissatisfied with the
intellectual power of their ancestorsexplanations, sought new
mythologies in their search for a better understanding of the
cosmos and their relationship with it.
Starting in the late 17th century, a new mythology arose in
Europe that was based on scientific principles and provided the
basis for a more reliable understanding of the relationship between
humans and sunlight. By the start of the 19th century, the
application of these principles led to the realization that sunlight is
not a single stimulus but, rather, a collection of stimuli of different
wavelengths (e.g. infrared, visible, ultraviolet). This realization
inspired additional studies aimed at determining whether different
wavelengths might be responsible for the different effects of
sunlight. As this review documents, indeed they are.
This review focuses primarily on studies before 1920 that were
involved in the discovery of UV radiation, its properties and its
influences on living organisms. After 1920, the number of UV-
related publications grew rapidly, reaching at least 275 for the
years 1920–1927 alone (1). Between 1960 and 2001, there are
37 466 publications on the subject ‘‘ultraviolet radiation’’ listed in
PUBMED, a U.S. government-supported computer database of
health-related research. Due to the extent of the literature, this
review covers only the most important studies between 1920 and
2001. The selection of these studies was made solely by the author,
and any omissions and shortcomings are his responsibility. There
are a number of excellent reviews on UV photobiology written
between 1920 and 2001, and these should be consulted for more
in-depth analyses (cf. [1–20]).
We begin with the discovery of UV radiation, its properties and
relationship with sunlight. These discoveries were unveiled
through a series of serendipitous observations coupled with
improvements in instrumentation and careful experimentation.
This is followed by a more detailed discussion of the evidence
linking sunlight and UV radiation with physiological and
pathological changes in humans, nonhuman animals and micro-
organisms. Each group has its own unique narrative relating it to
UV radiation. A recurring theme is that UV radiation has both
beneficial and harmful effects depending upon the type of
organism, wavelength region (UVA, UVB or UVC) and irradiation
dose (intensity 3duration).
THE DISCOVERY OF UV RADIATION,
ITS PROPERTIES AND RELATIONSHIP
WITH SUNLIGHT
The discovery of UV radiation and its properties was a gradual
process that spanned three centuries and involved scientists from
many countries (21–24). In 1614, Sala made a seminal observation.
He noticed that sunlight turned silver nitrate crystals black. In
1777, Scheele found that paper soaked in silver chloride solution
darkened when exposed to sunlight. When he directed sunlight
through a prism onto the paper, the violet end of the spectrum was
more effective than the reddish end.
In 1801, Ritter made the hallmark observation. He noticed that
invisible rays just beyond the violet end of the spectrum were even
more effective at darkening silver chloride–soaked paper. He called
them ‘‘deoxidizing rays’’ to emphasize their chemical reactivity
and to distinguish them from the ‘‘heat rays’’ at the other end of the
visible spectrum. Over time, the simpler term ‘‘chemical rays’’ was
adopted to describe these invisible rays along with the adjacent
violet-blue rays. The terms chemical and heat rays remained
popular throughout the 19th century, but they were eventually
dropped in favor of the more restrictive terms ultraviolet and
infrared radiation, respectively.
Initial studies of the chemical rays focused on their ability to
stimulate chemical reactions. In 1809, Gay Lussac and The´nard
demonstrated that concentrated sunlight was capable of converting
a mixture of hydrogen and chlorine gases into hydrochloric acid. In
1815, Planche´ noted that chemical rays darkened many kinds of
metallic salts. Between 1826 and 1837, Nie´pce and Daguerre found
that silver iodide was especially light-sensitive, and they used this
discovery as the basis for their early work in photography. In 1842,
Becquerel and Draper independently showed that when sunlight
was passed through a prism onto a daguerreotype plate (a gelatin
emulsion containing silver iodide), wavelengths between 340 and
{Posted on the web site on 1 October 2002.
*To whom correspondence should be addressed at: Department of
Physiology, M211, The Feinberg School of Medicine, Northwestern
University, 303 East Chicago Avenue, Chicago, IL 60611, USA. Fax:
312-503-5101; e-mail: p-hockberger@northwestern.edu
Abbreviations: BCE, before common era; CE, common era; CNS, central
nervous system; Hg, mercury.
Ó2002 American Society for Photobiology 0031-8655/01 $5.0010.00
561
400 nm induced a photochemical reaction. This was the first
indication of the spectral extent of UV radiation.
During the 19th century, physicists made several important
theoretical and empirical contributions that helped to clarify the
properties of UV radiation. In 1802, Wollaston expanded on
Newtons earlier observation that sunlight was composed of
different colors by showing that sunlight possesses discrete bands
of light rather than a continuous spectrum. In 1814, Fraunhofer
mapped over 500 bands of sunlight, later called ‘‘Fraunhofer
lines,’’ some of which are within the UV region. In 1859, Kirchoff
and Bunsen invented the spectroscope and demonstrated that
different atoms absorb and emit different wavelengths of light.
They speculated that the gaps in the solar spectrum are the result of
selective absorption by atoms in the Earths atmosphere.
A major breakthrough in photophysics came in 1865 when
Maxwell proposed a theory that light and sound are part of a lar-
ger spectrum of energy with wave-like properties. He called them
‘electromagnetic waves’’ because he believed that they were
generated by the interaction of electric and magnetic fields. In
1882, Maxwells theory was confirmed by Hertz who developed
a means for measuring microwaves, the first empirical evidence for
radiation beyond the UV–visible–infrared spectrum. His results
reinforced the belief that electromagnetic radiation travels in waves
at discrete frequencies (or wavelengths).
The development of artificial lighting provided another source of
UV radiation, although this was not appreciated at first. In 1808,
Davy invented the ‘‘open’’ arc lamp using charcoal electrodes
attached to a large Voltaic battery. Unfortunately, the charcoal
electrodes deteriorated in the process. In 1843, Foucault tried
carbon electrodes that were more stable, but the arc was dim. In
1876–1877, Jablochkov and Brush bolstered the power of carbon
electrodes using the Gramme dynamo and generated the first useful
electric arc lamps. In 1898, Bremer introduced fluoride salts into
the carbon electrodes that further enhanced their brightness. In
1850, Stokes used aluminum electrodes to produce a ‘‘closed’’ arc
lamp in a quartz tube that emitted UV rays to 185 nm. In 1835,
Wheatstone invented the mercury (Hg) vapor lamp, which was
brighter than previous arc lamps, but it was prone to flicker and
deterioration. It would take the contributions of many inventors
over the next 66 years before Cooper-Hewitt would produce the
first commercially viable Hg vapor lamp.
In 1802, Davy showed that artificial light was produced by
passing electrical current through a platinum wire. Although simpler
than the open arc lamp, it was not as bright. Nevertheless, in 1820,
De La Rue turned Davys observation into the first incandescent
light bulb. In 1879, Swan enhanced the brightness by using a thin
carbon filament instead of platinum wire. The same year, Edison
patented an incandescent lamp based on a thin cotton filament
encased in a partly evacuated tube. His lamp burned brighter and
longer (50 h) than any other incandescent lamp, and it soon replaced
arc lamps as the most popular form of artificial lighting. In 1906,
Coolidge invented the tungsten light bulb. Tungsten is more
malleable than other metals, allowing it to be coiled; with more
wire, it burned brighter and longer than other incandescent bulbs.
Tungsten also emits a broader spectrum than carbon-based
filaments, yielding a whiter (and more UV-intensive) light.
Another significant development in photophysics was the
invention of devices for quantifying radiation. In 1829, Nobili
invented the thermopile, and it was improved in 1852 by Melloni.
In 1876, Crookes invented the rotating vane radiometer, and in
1878 Langley invented the bolometer. All three inventions used
blackened metal to absorb radiation, but each device differed as to
how the radiation was quantified. The thermopile used a stack of
tightly packed metal plates to amplify the photoelectric signal. The
radiometer measured light intensity by the number of revolutions
induced over time, and the bolometer measured a decrease in
electrical resistance upon absorption of radiation. Each provided
an effective means of measuring radiation throughout the UV–
visible–infrared spectrum.
Early in the 20th century, new discoveries in photochemistry
and photophysics improved both theoretical and empirical under-
standings of the behavior of electromagnetic radiation. In 1900,
Planck theorized that radiation is composed of tiny packets of
energy called ‘‘quanta.’’ In 1905, Einstein theorized that Plancks
quanta were massless particles of energy (named ‘‘photons’’ in
1928 by Lewis) that are released from atoms and molecules upon
absorption of light. In 1913, Bohr proposed that electrons absorb
the light energy and reemit it at wavelengths that correspond to the
electrons energy. In 1926, Schro¨dinger developed a theory of
wave mechanics that treated electrons as waves rather than par-
ticles. These theories provided a new conceptual framework for
studies of radiation.
About the same time, experimentalists were devising new ways
to measure the extent of UV radiation. In 1903, Schumann used
a carbon spark discharge lamp and fluorite prism placed in
a vacuum chamber (called a ‘‘vacuum spectrograph’’) to detect the
emission of hydrogen at 120 nm. In 1906–1908, Lyman used the
vacuum spectrograph to detect emission of helium at 50 nm. He
also demonstrated that oxygen, but not nitrogen, absorbs radiation
between 127 and 176 nm. In 1920, Millikan used a high-intensity
nickel spark lamp in a vacuum spectrograph to measure the
emission of hydrogen at 20 nm. He also detected the emission of
weak X-rays indicating that there was no natural cut-off between
UV and X-rays.
Atmospheric scientists helped to establish the relationship
between sunlight and UV radiation. In 1902, Langley showed that
the Earths atmosphere reduces UV radiation by approximately 40
per cent. Based on Lymans results, Miethe and Lehman proposed
in 1909 that oxygen in the upper atmosphere absorbs most of the
UV radiation. They determined that the lower limit reaching the
Earths surface was between 291.21 and 291.55 nm. In 1921, Fabry
and Buisson measured the spectral composition of sunlight and the
absorption characteristics of ozone. They surmised that ozone in
the upper atmosphere is responsible for filtering most of the solar
UV radiation. In 1919, Dorno demonstrated that the intensity of
UV radiation penetrating the atmosphere varies throughout the day
(greatest when directly overhead) and with the seasons of the year
(greatest in summer).
By 1920, the existence of UV radiation, its properties and
relationship with sunlight was well established. The potential for
commercial and industrial applications shifted the focus to
development of new sources (fluorescent lamps, photoflash lamps,
stroboscopes, lasers, advanced photon source) and better devices
for measuring it (filters, detectors, spectrometers). Research on the
interaction of UV radiation with atoms, molecules, solutions and
the atmosphere continued. An example of the latter is the work of
Molina, Rowland and Crutzen, who have studied the destructive
effect of industrial pollutants on the ozone layer. There was also
increasing interest in understanding the effects of UV radiation on
living organisms, especially humans. The connection between
sunlight and UV radiation raised the possibility that many of the
effects of sunlight that had been observed over the centuries might
562 P. E. Hockberger
be due to these invisible rays. As revealed in the following
sections, there is ample evidence supporting such a connection.
(Note on terminology: During the 20th century, the study of UV
radiation led to the development of different terminologies.
Physicists developed a terminology based on the physical
properties of UV radiation. They adopted the term ‘‘near UV’’ to
refer to solar UV that reaches the Earths surface, i.e. 290–400 nm.
They used the term ‘‘vacuum UV’’ for the region that required
a vacuum to measure it, i.e. below 180 nm. They used the term ‘‘far
UV’’ for the region between the near and vacuum UV regions, i.e.
180–290 nm. Biologists developed a different terminology that
emphasized the effects of solar UV on living organisms. They used
the term ‘‘UVC’’ to refer to the solar region that was absorbed by
the ozone layer in the Earths upper atmosphere, i.e. below 290 nm,
and therefore had no biological effect. The term ‘‘UVA’’ was used
for the region 320–400 nm that penetrated window glass and had
physiological effects on organisms. The term ‘‘UVB’’ was applied
to the region between the UVC and UVA, i.e. 290–320 nm, and
this region was believed to be responsible for the deleterious
effects of sunlight on living organisms.)
HUMANS, SUNLIGHT AND UV RADIATION
Human fascination with sunlight undoubtedly began before the
dawn of civilization (25–30). Our hominid ancestors must have
recognized its importance for vision and warmth and, eventually,
agriculture. Given the suns importance and our ancestors
primitive understanding of the cosmos, it is not surprising that
they worshiped the sun. Hieroglyphic-, cuneiform- and alphabet-
based writings indicate that the sun was revered as a god by the
Egyptians, Assyrians, Persians and Babylonians between 3000 and
500 BCE. Archaeological and anthropological evidence suggests
that the sun was also deified by other ancient civilizations
including the Druids, Aztecs, Incas and American Indians. Even
the ancient Greeks, who were the first to write about the
importance of sunlight in human health, worshiped the sun god
Helios.
Around 400 BCE, two events of scientific importance occurred
in Greece. The Ionian philosopher Anaxagoras was put on trial for
promoting the idea that the sun is a big fiery rock, rather than
a deity, and the Athenian physician Hippocrates prescribed
heliotherapy (sunbathing) for both medical and psychological
purposes. These events initiated a change, albeit a slow one, in
human understanding of the relationship between sunlight and
living organisms.
The practice of heliotherapy continued throughout the Greco-
Roman era, and it appears in the writings of Herodotus (5th century
BCE), Cicero and Celsus (second century BCE), Vitruvius (first
century BCE), Pliny the Elder (23–79 CE), Galen (130–200 CE),
Antyllus (third century CE) and Oribasius (325–400 CE). After the
fall of the Roman Empire, the practice apparently fell into oblivion.
It reappeared during the Early Middle Ages, documented by the
Persian scholar and physician Avicenna (980–1037 CE). Sunbath-
ing for medical and cosmetic purposes has continued to the present
time due to a pervasive cross-cultural belief in the healing power of
sunlight. As outlined in the following section, early scientific
studies supported and reinforced this belief.
The health-promoting influence of sunlight
Although heliotherapy has been practiced for at least 2400 years,
there was very little objective evidence supporting its purported
therapeutic influence. By the 18th century, reports began to appear
in the medical literature indicating that sunlight ameliorated
different skin diseases. In 1735, Fiennius (cited in 31) described
a case in which he cured a cancerous growth on a patients lip
using a sunbath. In 1774, Faure (cited in 30) reported that he
successfully treated skin ulcers with sunlight, and in 1776 LePeyre
and LeConte (cited in 28) found that sunlight concentrated through
a lens accelerated wound healing and destroyed tumors.
There were also reports that sunlight had beneficial effects on
internal maladies. In 1782, Harris (cited in 31) used irradiated
mollusk shells to improve a case of rickets (fragile bones). In 1815,
Loebel (32) used facial irradiation to heal a case of amaurosis
(partial blindness caused by disease of the optic nerve), and in
1845, Bonnet (33) reported that sunlight could be used to treat
tuberculosis arthritis (bacterial infection of the joints). In 1879,
Martin (34) used stripes of blue and white light to treat progressive
degeneration of the optic nerve.
Additional observations indicated that sunlight was capable of
altering basic human physiology. In 1843, Scharling (35) measured
reduced production of CO
2
in subjects at night, and in 1866 von
Pettenkofer and Voit (36) reported that serum bicarbonate levels
were lower at night. In 1850, Berthold (37) found that hair
production was greater in the daytime, and in 1888 Fere´ (38) noted
that breathing and pulse rate were reduced under red light. These
results were supported by similar data from animal studies (see
below), but it would be well into the 20th century before the notion
of daily (circadian) rhythms would take hold.
Probably the most remarkable claim during this period was the
positive influence of sunlight on mental health. This idea can be
traced back to Hippocrates (cited in 39) who recognized that
depression was more common in the winter months in Greece
when there was less sunlight. In 1806, Pinel (39) identified two
types of seasonal depression, one occurring in winter and another
in summer. By 1845, his student Esquirol (39) documented several
cases of both types of depression. In 1876, Ponza (40) reported that
light therapy was beneficial for treating patients with mental
illness. In particular, he found that violet-blue light was useful for
reducing mania, whereas red light improved depression. During the
20th century, phototherapy would be rediscovered several times
as an effective means for treating seasonal affective disorders
(41–43).
One of the earliest indications that sunlight might have
detrimental effects involved cases of smallpox. It had been known
for centuries that sunlight aggravated smallpox, although the origin
of this connection is unknown. By the time the son of Edward I of
England (1239–1307 CE) contracted the disease, it was standard
practice to cover patients and windows with scarlet sheets and
blankets (29). This remedy was widely known and documented
as far away as China and Japan during the Middle Ages. Never-
theless, there was virtually no scientific assessment of its effective-
ness until the 19th century.
In 1832, Picton (44) was the first to document the detrimental
effects of sunlight on patients with smallpox. He reported that
soldiers confined to dungeons during a smallpox epidemic con-
tracted the disease but recovered without suppuration or scarring.
In 1848, Piorry (45) recommended keeping patients with the dis-
ease in darkened rooms until the disease passed. In 1867, Black
(46) found that exclusion of sunlight slowed the development of
the pustules of smallpox and prevented pit formation. By 1871,
Waters (47) and Barlow (48) independently confirmed the posi-
tive results of light deprivation on patients with smallpox under
Photochemistry and Photobiology, 2002, 76(6) 563
controlled conditions. They noted that the treatment was more
effective if started early in the disease before eruptions. In 1898,
Chatinie´re (49) used similar red light therapy to treat measles.
Despite the widespread success of red light therapy, there was no
agreement as to how it worked. In 1893, Finsen (50) speculated
that the chemical rays were detrimental to smallpox patients,
although he provided no evidence for this or offered any
explanation as to how such rays might aggravate the disease.
Four years later, he showed that chemical rays had the opposite
effect in the treatment of lupus vulgaris (cutaneous tuberculosis). In
this case, he demonstrated that the chemical rays from sunlight or
an arc lamp had antibacterial actions (see section below on
microorganisms) and that, under appropriate conditions, it cured
the disease. For this accomplishment, he was awarded the 1903
Nobel Prize in Physiology or Medicine and endowed with financial
support for the Finsen Light Institute in Copenhagen.
Diagnostic uses of light
The prospect of using light for diagnostic purposes was initiated by
Richardson in 1868 (cited in 51). Using various light sources, most
notably a magnesium arc lamp, he showed that light was
transmitted through the more lucent structures of living and dead
bodies. Absorption of light by internal structures allowed him to
view the obscure outlines of bones of the hand and foot and
structures within the cheeks, neck, chest and abdomen. Even
pulsations within blood vessels were visible although the vessels
themselves were indistinct. In an extremely emaciated young
subject, the beating of the heart was faintly discernable although
the motions of the heart valves were not. He also made similar
observations of structures in a frog, chick and carp. In 1870,
Nicholson (51) succeeded in viewing internal organs of the human
body using a calcium lamp.
In 1898, Gebhard (52) used an arc lamp and daguerreotype plate
to show that light can penetrate the human body. He placed the
plate in the palm of his hand and shielded it from light with plaster
of Paris. When the back of his hand was exposed to the lamp, the
plate darkened demonstrating that light had passed completely
through his hand. In 1901, Darbois (53) demonstrated that a piece
of photographic paper, placed between two glass slides and
inserted into the mouth and then irradiated with an arc lamp
through the cheek, became blackened after 1 min. The previous
year, Kime (54) showed that sunlight was capable of producing an
image on a photographic plate after passing completely through the
thorax. Despite these successes, the discovery of X-rays by
Ro¨ntgen in 1895 and its incredible resolution shifted attention
away from light as a diagnostic tool. It would reappear in the late
20th century, however, with the invention of optical coherence
tomography (55).
The dark side of sunlight and arc lamps
Despite numerous observations on the growth-promoting and
healing effects of sunlight, the underlying physiology was poorly
understood. For centuries, conventional wisdom assumed that the
warmth of sunlight simply accelerated the natural growth and
healing powers of the body. Negative effects, like sunburn
(erythema) and blindness caused by sungazing (solar retinopathy),
were believed to be due to excessive exposure to the suns heat. In
1821, Home (56) was the first person in the modern era to openly
question this assumption. He argued that sunburn to the back of his
hand was not caused by the heat rays of the sun because covering
the opposite hand with a black cloth prevented the response even
though the air temperature under the cloth was 6–88F warmer.
Furthermore, he found that illumination of the hand of a Negro
failed to elicit sunburn even though the temperature of the Negros
skin increased by the same amount as his own.
Home was clearly puzzled by his results. He mentioned that he
had experienced a severe burn on the back of his legs 40 years
earlier during a voyage to the West Indies. This occurred despite
the fact that he was wearing a thin pair of linen trousers. He stated
‘I could not image how it happened, always suspecting it to be the
effect of the bites of insects; but I never satisfied myself upon that
subject.’’ Armed with his new results, he surmised that both burns
were caused by the sun but not by the heat rays. He reasoned that
black skin somehow provided a protective shield against sunburn.
When he asked Sir Humphrey Davy for his interpretation of the
results, Davy concluded that the radiant heat of sunlight was
absorbed by black skin and converted into ‘‘sensible’’ heat. There
was no indication as to what Davy meant by sensible, but this was
likely an attempt to bring Homes results in line with the
conventional wisdom.
Evidence that UV rays could be harmful to people came initially
from scientists working with arc lamps. In 1843, Fizeau and
Foucault (57) reported problems with their eyes after experiment-
ing with a carbon arc lamp, and they suspected that it was caused
by the chemical rays. In 1859, Charcot (58) noted that arc lamps
caused skin burns, and he too believed it was due to the chemical
rays. In 1889, Maklakoff (59) reported that welders experienced
irritation of the eyes and skin within a few hours of exposure to
high-intensity welding arcs. He noted a progression of effects
including acute flu-like symptoms, erythema, pain and delayed
pigmentation.
In 1889, Widmark (60,61) published his landmark studies
confirming that UV rays from arc lamps were responsible for skin
burns. He showed that burns were induced by the chemical rays of
a carbon arc lamp transmitted through a prism and filtered through
water to remove the heat rays. Furthermore, burns were avoided if
the lamplight was filtered through window glass, indicating that
rays below 320 nm were the primary culprits. These results were
extended in 1891 by Hammer (62), who found distinct differences
between sunburn caused by chemical and heat rays. He showed
that heat rays caused redness of the skin that appeared quickly and
disappeared shortly after exposure (within minutes). Chemical
rays, on the other hand, caused redness that appeared several hours
later, was persistent, and was followed by desquamation (loss of
skin) and eventually increased pigmentation. These results were
confirmed by Hausser and Vahle (63) in 1927, and they produced
the first detailed action spectra for erythema and pigmentation.
Other investigators documented changes in skin attributed to the
chemical rays of sunlight. In 1885, Unna (64) found that sun-
exposed skin was thicker and displayed enhanced keratinization. In
1890–1892, Berliner (65) and Wolters (66) declared that chemical
rays were responsible for sunburn, xeroderma pigmentosum and
Hutchinsons summer eruptions. By 1894, Unna (67) was con-
vinced that UV and, possibly, the violet-blue rays of sunlight
were responsible for increased skin thickness, pigmentation and
skin cancer in sailors. In 1896, Dubreuilh (68) reported that people
with outdoor (rural) occupations were more prone to skin cancer
than those with indoor (urban) occupations.
There were also reports of people who were unusually
susceptible to sunburn. In 1886, Veiel (69) reported a case of
564 P. E. Hockberger
a woman who became sunburned through a window glass. Because
she was protected by a red veil, Veiel concluded that it was caused
by the suns chemical rays. In 1898, Anderson (70) reported that
two patients exhibiting seasonal sunburn (hydroa aestivale)
possessed an unusual porphyrin-like pigment in their urine.
Ehrman (71) suggested that this pigment was hematoporphyrin,
although Gu¨nther (72) noted that not all patients with porphy-
rinuria were light-sensitive. In 1913, Meyer-Betz (73) confirmed the
photosensitizing properties of hematoporphyrin by administering it
to himself.
The safety of arc lamps and sunbathing is debated
By the start of the 20th century, additional reports questioned the
safety of arc lamps and the healthiness of sunbathing. Moeller (74)
demonstrated that continuous exposure of skin to an arc lamp
caused a sequence of changes that included vasodialation, swelling
of the extracellular space, hyperplasia of the epidermis and an
abnormal horning process. Hyde (75) described similarities in the
damaging action of UV rays, X-rays and radium exposure on skin,
and he presented epidemiological data suggesting that sunlight
causes skin cancer.
In 1916, Burge (76) argued that glass blowers cataracts, caused
by arc lamps, are due to absorption of UV rays by the lens proteins
leading to their precipitation. The same year, Verhoeff and Bell
(77) showed that cataracts are caused by an indirect process
initiated by the heat rays of the arc lamp. They found that
absorption of heat caused damage to the ciliary body leading to
malformation of the lens. In 1920, Van der Hoeve (78) showed that
absorption of UV rays had the same effect, i.e. damage to the
ciliary epithelial cells, interfering with the nutrition of the lens. By
1922, Schanz (79,80) argued that both infrared and UV rays are
responsible for the cataracts of glass workers.
Despite these observations, many health professionals, especi-
ally those working at the Finsen Light Institute, continued to extol
the virtues of heliotherapy as long as protective eyewear was used.
Their advice was bolstered by a growing list of diseases that could
be treated with heliotherapy including verrucose tuberculides,
lupus erythematosus, alopcia areata, acne vulgaris and naevus
vascularis planus (50). In addition, investigators from outside of
the Finsen Institute obtained positive results with light therapy.
Schouli (81) and Festner (cited in 82) used red light to reduce the
severity and duration of scarlet fever and skin inflammation
(erysipelas). Bernhard (cited in 83) and Rollier (83) used Alpine
sunbaths to heal wounds and surgical (extrapulmonary) tubercu-
losis. Hasselbalch and Jacobaus (84) used a carbon arc lamp to
treat cardiac afflictions, and Huldschinsky (85) used sunbaths and
UV rays from an Hg arc lamp to treat rickets. By 1924, Hess
(86,87) and Steenbock (88) and their colleagues had independently
shown that sunlight cured rickets by inducing vitamin D
production in the skin.
Light was also used successfully to treat diseases of the eye.
Nesnamov (cited in 89) used sunlight through a collecting lens to
treat corneal ulcers. Nicolas (90) used sunlight to treat conjunctival
tuberculosis and an Hg arc lamp to treat scrofula and tuberculosis
of the outer eye. Schanz (80) confirmed Nicolass results and added
eyelid eczema to the list of eye diseases treatable with light. Duke-
Elder (91) showed that UV rays were effective for treating
tubercular and inflammatory eye conditions involving the con-
junctiva, cornea, iris, ciliary body, choroids and retina. By 1923,
Wright (92) recommended using concentrated sunlight or artificial
light to treat trachoma and corneal ulcers.
Although the above studies focused on the therapeutic effects of
light therapy, other investigators studied the bodys natural
adaptive responses to sunlight. In 1901, Ehrmann (93) reported
that skin tanning arises from local stimulation of melanin pro-
duction inside specialized skin cells (melanoblasts). In 1916,
Ju¨ngling (94) showed that melanin production was enhanced by
light rays longer than 330 nm, whereas sunburn was induced by
rays below 330 nm. In 1920, With (95) argued that skin thickening
helps protect against the damaging effects of UV rays, and Rollier
(83) reported that heliotherapy for surgical tuberculosis was more
effective in tanned people. These results were interpreted as
evidence that the body is endowed with natural mechanisms for
regulating the amount of light exposure.
Rollier also noted that heliotherapy was accompanied by
increased lymphocyte production (lymphocytosis) suggesting
a potential beneficial effect of sunlight on the immune system.
This observation was consistent with evidence obtained by
Wickline (96) and Chamberlain and Vedder (97) between 1908
and 1911 that showed that lymphocytosis developed gradually
over many months for Americans living in the Philippines. In
1919, Taylor (98) reported that 25 of 38 adults at a summer retreat
in Massachusetts (USA) displayed an increase in lymphocyte
production. Although these studies did not control for other
environmental variables (e.g. climate and lifestyle changes),
Aschenheim (99) demonstrated that exposure of infants to direct
sunlight, for as little as 1 h, resulted in lymphocytosis. There was
also compelling evidence from animal studies that supported these
claims (see below).
By 1920, the overriding consensus was that sunlight had
a positive influence on health. According to Laurens (1), ‘‘at one
time there was considerable argument as to whether ultra violet
radiation could act directly on deep seated organs, and there are
still some who believe that this is the case. The only reasonable
conclusion, however, is that following ultra violet irradiation some
photochemical substance formed in the skin is carried by the blood
stream to these various organs, there bringing about the observed
changes.’’ He continued ‘‘the sun bath by dilating the capillaries
activates the circulation and may induce a continuous tonic action
on the sensory nerve terminals in the skin, thus restoring tone to
muscles and promoting physiologic processes throughout the body.
This is the probable explanation of the increased metabolism of the
body, of the improvement in general health and of the increased
resistance to disease.’
The possibility that sunlight and its associated UV rays might be
harmful to humans did not take hold until later in the 20th century.
This change in attitude was influenced by four main factors. First,
experimental studies using animals and microorganisms provided
compelling evidence of the damaging effects of UV rays, as
described in the following sections. Second, evidence emerged that
other kinds of radiation (e.g. X-rays, gamma rays) had deleterious
effects on living organisms fostering the belief that all forms of
radiation are harmful. Third, governmental agencies were
established with the responsibility of supporting health-related
research, and they took a proactive role in funding investigations
that studied the pathological effects of UV radiation. Fourth,
additional epidemiological data indicated a correlation between
skin cancers and excessive exposure to sunlight. The collective
influence of these four factors eventually shifted the opinion of the
scientific community and the public. By the end of the 20th
Photochemistry and Photobiology, 2002, 76(6) 565
century, exposure to direct summer sunlight for extended periods
was considered a health risk.
ANIMALS, SUNLIGHT AND UV RADIATION
Physiological effects
Experimental investigation of the influence of sunlight on animals
began in the early 19th century. As with the human studies, the
earliest observations indicated that sunlight exerted a positive
influence on animal health including enhanced growth, develop-
ment, respiration and metabolism. In addition, there were
physiological studies of the effect of light on contractile tissues,
skin pigmentation, immune response and biological rhythms.
There was much interest in whether these effects were mediated
directly through the skin or indirectly through the central nervous
system (CNS) via the eyes. There was only occasional mention of
phototoxic or photophobic responses, although this possibility was
vigorously investigated during the 20th century.
Growth and development. In 1824, Edwards (100) reported that
sunlight enhanced the rate of development of frog eggs. Twenty-
six years later, Higginbothom (101) showed that development of
frog and salamander eggs progressed normally in the dark as long
as temperature was controlled. In 1858, Beclard (102) found effects
of light that were not as easy to explain. He noted that eggs of the
common house fly, Musca, developed faster under violet-blue light
compared with green, yellow, red or white light; furthermore,
green light inhibited their development. In 1874, Schnetzler (103)
found that green light also hindered the development of frog eggs.
In 1878, Yung (104) reported that violet-blue light increased
development and metabolism of frog, turtle and snail eggs,
whereas red and green light hindered them. In 1880, Schenk (105)
found that tadpoles obtained from eggs incubated under red light
were more motile than those obtained from eggs incubated under
blue light.
In addition to studies of egg development, there were reports on
the effect of light on the growth of animals. In 1871, Po¨ey (106)
reported that General Pleasanton had performed experiments
showing that piglets grew faster under violet light compared with
white light. In 1874, Hammond (107) noted that a 20 day old cat
kept in the dark for 10 days weighed less than its littermate even
though it had weighed more initially. After 5 days in normal
lighting, the light-deprived cat weighed the same as its littermate.
In 1900, Borissow (108) found that dogs and rabbits grown in light
weighed more at the end of a month than those grown in dim light.
In 1924, however, Degkwitz (109) was unable to show any effect
of light on the growth of puppies so long as their diet and exercise
were carefully controlled.
In general, the above studies indicated that light had a stimula-
tory effect on growth and development, although it depended upon
the color of the light. The most consistent stimulatory effects were
obtained with violet-blue light, although the quality of the filters
(usually liquids) and the intensities of the light were not addressed.
Nevertheless, additional studies demonstrated other positive effects
of chemical (UV and violet-blue) rays on living organisms, as
described below.
Respiration and metabolism. In 1858, Beclard (102) noted that
violet-blue light enhanced CO
2
production in adult frogs but not in
the birds or mammals he tested. In 1870, Selmi and Piacentini
(110) reported that yellow light enhanced CO
2
production in a dog,
hen and turtle. In 1872, Chassanowitz (111) confirmed Beclards
results using frogs and further showed that it was not due simply to
enhanced motor activity during illumination. In 1875, Von Platen
(112) found that illumination of the frog retina stimulated oxygen
uptake, CO
2
production and increased metabolism. The same year,
Pott (113) showed that an individual mouse produced more CO
2
under green or yellow light than under violet, red or sunlight. It
also produced less CO
2
at night.
In 1879, van Pesch (114) found that pea beetles exposed to light
consumed more oxygen than those in the dark. Two years later,
Fubini (115) reported that frogs illuminated after lungectomies
generated less CO
2
than normal frogs, indicating that the effect was
not just a local skin response. The same year, Moleschott and
Fubini (116) reviewed the literature and concluded that violet-blue
light enhanced CO
2
production in amphibians, birds and mammals.
They surmised that blinded animals produced less CO
2
during
illumination and that both the respiratory rate and tissue respiration
were affected. In 1885, Moleschott (117) reported that light-
induced CO
2
production in frogs was mediated locally through the
skin as well as through the visual system. By 1887, Fubini and
Spallitta (118) showed that all colors were effective at increasing
CO
2
production, though not to the same degree.
Vision and CNS involvement in light responses. In 1883,
Lubbock (119) showed that ants are able to see UV rays, and in
1914 Van Herwerden (120) found that Daphnia (water fleas)
responded to rays shorter than 334 nm. In 1924, von Frisch (121)
demonstrated that bees can perceive rays at 300 nm, and Lutz (122)
confirmed that bees, wasps and fruit flies see UV rays. In 1924–
1925, Schiemenz (123) and Wolff (124) provided evidence that
fish can see the 365 and 340 nm lines of an Hg arc lamp. Recent
evidence indicates that some birds are also capable of UV vision
(125) and that insects (126) and fish (127) are endowed with the
ability to perceive UV polarized light.
In 1922, Shoji (128) measured the extent of UV absorption by
the cornea in 11 different kinds of animals (including man) and
showed that it absorbs UV rays shorter than 300 nm. He found the
average peak absorption of the lens was 366 nm and that
substantial UV rays were transmitted to the retina in some animals.
Mayer and Dworski (129,130) used UV rays from a Hg vapor lamp
to treat experimentally induced corneal tuberculosis in rabbits and
guinea pigs. Under virtually identical conditions, they found the
treatment effective in the rabbits but not in the guinea pigs,
indicating species differences in the effectiveness of the treatment.
Although the importance of the retina in vision and its
anatomical connection to the CNS were well known by the 19th
century, the visual transduction process was not understood. In
1866, Schutze (cited in 31) demonstrated that vertebrate eyes
possess two kinds of photoreceptors: rods for dim vision and cones
for color vision. In 1877, Boll (131,132) and Ku¨hne (133,134)
independently published their classical studies on visual purple
(rhodopsin), the photoreceptor pigment of rods, and established
that it was involved in the detection of light. Sixty years later,
Hosoya (135) showed that rhodopsin absorbs UV as well as visible
rays. Although UV rays are substantially absorbed by the cornea
and lens, recent evidence indicates that they can affect mate choice,
communication, foraging for food and circadian rhythms (136; also
see Indirect Effects [Photosensitization], below).
Several investigators studied the influence of light on blinded
animals. In 1876, Fubini (137) showed that blinded frogs put on
more weight than normal frogs when both were raised under
identical lighting conditions. Both groups displayed accelerated
weight gains when light exposure was discontinued. In 1878, Bert
(138) confirmed Fubinis results, and in 1879 Wedensky (139)
566 P. E. Hockberger
demonstrated that blinded frogs oriented their heads towards the
light source so that both halves of their body received equivalent
exposure. Upon decapitation, he showed that frogs experienced
heightened spinal reflexes on the side facing the light. In 1888,
Wedensky (140) reported that Golowin had discovered that light
and heat enhance spinal reflexes in the frog.
In 1883, Graber (141) showed that blinded salamaders and
naturally blind ringworms avoided UV and violet-blue light, and
he suggested that the response was mediated through the skin. In
1890, Dubois (142) confirmed that blinded salamanders displayed
an aversion to shorter wavelengths of light, and, in 1895, Finsen
(50) extended the results to frogs, earthworms, woodlice, beetles
and flies. Around the same time, Loeb (143) and Hesse (144)
reported that planarians (flatworms) move away from intense
visible light, and Parker and Burnett (145) showed that even
blinded planarians are negatively phototaxic. Agreeing with
Graber, they believed that the response was mediated through
the skin.
Contractile tissues. Several studies showed that light stimulated
the motility of contractile tissues. Between 1844 and 1859, Arnold
(146), Reinhardt (147) and Brown-Sequard (148) observed that
artificial light induced contraction of the iris muscle in the
extracted eyes of eels and frogs. Brown-Sequard further demon-
strated that it was due to a direct effect of light on the pupillary
sphincter muscle. In 1892, Steinach (149) extended these results to
fish and amphibians by showing contraction of the papillary
muscle in response to light in isolated eyes even after carefully
removing the optic and oculomotor nerves.
In 1857, Marme´ and Moleschott (150) found that communica-
tion across the frog neuromusclular junction was enhanced by
light. In 1879, Uskoff (151) noticed that spontaneous ciliary
movement of isolated frog epithelial cells was momentarily
stopped when illumination of the cells was changed from violet-
blue to red light but not by red light alone. In 1905, Dreyer and
Jansen (152) reported that UV rays caused capillary stasis in the
frogs web, tongue and mesentery. In 1924, Campbell and Hill
(153) obtained similar results using mesenteries of the frog and
mouse.
Other studies demonstrated wavelength-dependent responses in
excitable cells. In 1919, Adler (154) showed that UV, but not
visible, rays stimulated smooth muscle contraction in the frog,
rabbit and guinea pig. In 1954, Giese and Furshpan (155) showed
that low-intensity UV rays increased the frequency of discharge of
the stretch receptor of a crayfish muscle, whereas high-intensity
UV rays decreased it. In 1957, Pierce and Giese (156) found that
high-intensity UV rays reduced the amplitude of action potentials
in the axons of frogs and crabs, but irradiation with blue light
immediately afterwards reversed the effect (photoreactivation). In
1971, Fork (157) used violet-blue and green laser light to stimulate
action potentials in slug neurons without causing permanent
damage to the cells. Recently, Yuste and colleagues (158) have
achieved the same result in mammalian neurons using an infrared
laser and two-photon absorption in the violet-blue region.
Skin pigmentation. It is well known that chameleons become
darker when exposed to direct sunlight. In 1852, Bru¨cke (159)
showed that this was the result of pigment cells moving to the
surface, and he surmised that the response was mediated through the
visual system. Shortly thereafter, Wittich (160) reported that frog
skin became lighter in sunlight, the opposite of chameleons. In 1858,
DuBois-Reymond (161) found that the skin of the electric catfish,
like frog skin, became brighter in sunlight and turned black in the
dark. In 1874, Pouchet (162) found similar results with other types of
fish raised in darkness. He also noticed that fish with cataracts
(clouded corneas) were darker than their peers, suggesting
involvement of the eyes in the production of pigmentation. In
1875, Bert (163) confirmed Bru¨ckes observations on chameleons,
but he proposed that it was caused by a local effect on the skin rather
than mediated through the eyes (i.e. CNS). Bert (163) and Hoppe-
Seyler (164) both showed that chameleons are more responsive to
blue light than red or yellow light, indicating that changes in
pigmentation were unlikely to be due to changes in skin temperature.
Immune system. The effect of light on the immune system was
first reported by Kondratieff (165), who showed that violet and
white light enhanced recovery of sepsis-induced infection in
rabbits. Furthermore, he found that light increased the severity of
sepsis-induced cramps as well as caused an increase in body
temperature. When sepsis was severe, he noticed that violet and
white light paradoxically decreased the animals body temperature.
As with humans, sunlight stimulates lymphocytosis in animals.
In 1908, Polito (166) detected lymphocytosis in rabbits exposed to
direct sunlight for as little as 15 min. In 1921, Clark (167) found
similar results with rabbits whose ears were shaved and irradiated
with an iron arc lamp for 1 h. She showed that there was an initial
transient drop in lymphocytes within the first few hours after
irradiation, followed by an increase that reached a maximum 5
days after exposure, followed by recovery by the ninth day.
Although all wavelengths between 230 and 750 nm induced the
initial transient decrease, the subsequent increase was obtained
only with rays between 230 and 320 nm. Whole blood irradiated
outside the body and reintroduced showed no such effect. She
proposed that UV rays produced a ‘‘cutaneous reflex’’ that
stimulated lymphocyte-producing organs via the blood stream.
Some investigators speculated that lymphocytosis helps to
explain both the positive and negative effects of heliotherapy in
humans. In 1919, Murphy and Strum (168) demonstrated that mice
with lymphocytosis show a high degree of immunity to certain
transplantable tumors as well as enhanced resistance to bacterial
infection. Around the same time, Levy (169,170) and Gassul (171)
reported that UV irradiation of mice between 10 min and 56 h
caused progressive engorgement of internal organs (especially the
spleen) with blood. Clark (167) suggested that this may explain the
lung hemorrhaging that was frequently seen after heliotherapy for
tuberculosis.
Biological rhythms. The first evidence of biological rhythms
originated with the study of plants. In 1729, De Mairan (cited in
172) showed that leaves display periodic movements even in
complete darkness that corresponded to day–night cycles. Further
studies by many investigators confirmed and extended these
results, as reviewed by Bunning (173). The earliest evidence of
light-dark cycles in animals was provided by Kiesel (174) in 1894.
He described cyclical changes in arthropod pigmentation that
persisted in the dark. Thirty years later, Marcovitch (175) found
that the sexual development of aphids is dependent upon the length
of daylight.
Between 1926 and 1932, Bremer (176) showed that pupation in
insects is dependent upon light–dark cycles, Beiling (177)
demonstrated that the activity of bees is dependent upon the time
of day, and Bisonette (178) showed that the breeding behavior of
ferrets is dependent upon the length of daylight. Rowan (179)
reported that increased daylight enhances gonad development in
the migratory junco bird. These results and others led Bunning
(180), in 1936, to propose the concept of an endogenous biological
Photochemistry and Photobiology, 2002, 76(6) 567
clock in animals modulated by daily cycles of light and dark. In
1959, Halberg (cited in 181) coined the term ‘‘circadian rhythms’
to describe these cycles.
Until recently, most scientists believed that circadian rhythms in
mammals were modulated only by visible rays. In 1987, Brainard
and colleagues (182) demonstrated that UVA rays suppressed the
nocturnal production of melatonin in mice, and in 1994 (183) they
showed that UVA rays altered murine neuroendocrine and
circadian rhythms. In 1995, Amir and Robinson (184) showed
that UVA rays are capable of inducing phase shifts in the
expression of a transcription factor (Fos) in the hypothalamus of
the rat. Very recently, Berson, Yau and colleagues (185,186) have
demonstrated that rat retinal ganglion cells are photosensitive, due
to the photosensitive pigment melanopsin that absorbs throughout
the UV and visible spectrum, and that these cells are responsible
for setting the circadian clock.
Cultured cells. During the past decade, several groups have
shown that irradiation of cultured cells with UV rays activates
genes that influence cell division and immune responses. The
activatable genes include plasminogen activator (187), interleukin-
1 (188), c-fos (189), small proline-rich proteins (190), growth
arrest and damage-inducible proteins (191), multi-drug resistance
one gene (192) and p53 (193). Many of the UVC-inducible genes
are activated by a transcription factor complex involving either AP-
1, NFkB or p53 protein (194). In some cases, UVB and UVA rays
induced similar responses. It remains unclear, though, whether
these responses reflect physiological responses to UV rays or
pathological effects due to cell injury.
Pathological effects
The possibility that sunlight and artificial sources of UV radiation
might be harmful to nonhuman animals did not arise in force until
the 20th century. Nevertheless, there were isolated reports in the
previous century of inhibitory effects of light. As mentioned above,
Beclard (102), Schnetzler (103) and Yung (104) noticed that green
light inhibited the growth and development of both vertebrate and
invertebrate eggs, although the spectroscopic properties of the
filters were not described. Graber (140), Loeb (143), Hesse (144)
and Finsen (50) reported that various vertebrate and invertebrate
animals avoided UV and violet-blue light if the intensity was too
high. In 1882, Marshall (195) noticed that the motile larvae of
sponges accumulated on the side of the tank with less light, and 3
years later Ultzmann (196) found that isolated sperm survived for
48 h if protected from cold and light.
Early in the 20th century, the debate in the literature over the
healthiness of heliotherapy and arc lamps provided the motivation
for testing these ideas using animal models. The following studies
are examples of pathological responses in animals that were induced
by exposure to UV rays. In most cases, the investigators employed
high-intensity artificial lights (arc lamps, fluorescent lamps, lasers)
whose spectral emissions were enriched in UV rays. In these cases,
the relevance of the results to sunlight is often unclear.
Circulatory and immune system damage. Campbell and Hill
(153) reported that UV rays from either a carbon arc lamp or a Hg
vapor lamp projected through a lens onto frog or mouse mesentery
caused localized stasis in capillaries independent of temperature
changes. Similar results were obtained with visible light if the
tissue was bathed in eosin or hematoporphyrin. The latter induced
the formation of thrombii and localized leukocytosis, whereas UV
rays alone induced only leukocytosis.
Chronic low-dose solar-simulated UV radiation can cause both
local and systemic immunosuppression (197,198). This has been
shown using either UVA or UVB rays. Suppression of the immune
system may permit the outgrowth of UV-induced skin tumors.
Reproductive system damage. In 1928, Altenburg (199) dem-
onstrated that UV rays cause mutations in fruit flies if the rays
reach the reproductive organs. One can only wonder whether other
insects that are equally unprotected from sunlight and UV radiation
are susceptible to similar damage and whether solar-induced
mutations contribute to evolutionary changes.
Skin cancer. In 1928, Findlay (200) reported that skin tumors
developed in depilated albino mice exposed for 8 months to UV
rays from a quartz Hg vapor lamp. Exposure of mice to the
combination of UV rays and coal tar produced skin tumors in only
3 months. In 1934, Roffo (201) demonstrated that skin cancer
could be induced in rats by exposure to either sunlight or Hg arc
lamps. In 1936, Funding et al. (202) found that 290–320 nm
(UVB) was the region of sunlight most responsible for inducing
tumors in experimental animals. These results coincided with
Latarjets (203) proposal that changes in atmospheric ozone levels
could increase the risk of skin cancer.
In 1941, Blum and associates (204,205) reported that skin cancer
could be reproducibly induced in the ears of mice exposed to UV
rays from arc lamps. A single exposure was insufficient, and cancer
developed over time in a predictable fashion. Total irradiation dose
was important but not the exposure interval (reciprocity held).
Only wavelengths below 320 nm worked. Unlike humans, dermal
tumors in mice were common. The authors speculated that this
could be due to the greater UV penetration of mouse skin. In 1943,
Bain and Rusch (206) showed that UV rays are more effective in
producing tumors in mice when given at low intensities over long
periods rather than at high intensities over short periods.
In 1975, Freeman (207) irradiated mice with a monochrometer at
intervals between 290 and 320 nm and produced the first action
spectrum for skin cancer. Using daily dosages equivalent to the
threshold dose for erythema production in untanned human skin,
he found that the peak carcinogenic response occurred at 310 nm.
His results supported the hypothesis that the carcinogenic
effectiveness of UV rays is proportional to the erythema effec-
tiveness. He speculated that the two effects may have a common or
similar site of action.
In 1976, Zigman and colleagues (208) showed that longer
wavelength UV rays from a ‘‘black light’’ are capable of inducing
skin cancer in mice, a result confirmed by Strickland (209), who
also noted that UVA rays were far more carcinogenic when
combined with UVB. In 1993, Setlow et al. (210) reported that
UVA and violet light (420 nm) from high-intensity lamps are
capable of inducing cutaneous malignant melanoma in fish. In
1994, De Gruijl and van der Leun (211) calculated that skin cancer
in hairless mice and humans occurs over a broad region of the solar
spectrum with peaks at 300 and 380 nm, the shorter wavelength
region approximately 1000-fold more effective.
The possibility that sunlight can cause mutations in skin cells
leading to skin cancer has been supported by studies of tumor
biopsies in humans and animals. Brash and colleagues (212,213)
found mutations in the p53 gene in nonmelanoma tumors in
humans, and De Gruijl and associates reported similar mutations in
mouse skin irradiated with UVB rays (214). Quantitative studies
suggest that this mutation is present in approximately 50% of
human basal cell carcinomas and 15% of squamous cell
carcinomas (212,215). The incidence of tumors with p53 mutations
568 P. E. Hockberger
is much higher in mice exposed to UVB rays, but approximately
the same in mice exposed to UVA rays (216). Because the p53
gene controls cell cycle regulation, a loss of function mutation in
this gene could be an early event in the initiation of nonmelanoma
skin cancers.
Damage to cultured cells. Several investigators have noted that
illumination of cells through a microscope caused deleterious
effects. In 1879, Uskoff (151) noted that isolated white blood cells
displayed greater outgrowth of processes during microscopic
examination with red light compared with violet-blue light. In
1915, Lewis and Lewis (217) found that the mitochondria of
embryonic chick cells degenerate after 15 min of microscopic
observation. They also noted that the mitochondria-specific dye
Janus green was toxic even in the absence of light. In 1916,
Macklin (218) reported that cultures of embryonic chick heart
degenerate quickly when illuminated through a microscope using
daylight, tungsten globe or a Welsbach burner. Degeneration was
exacerbated in the presence of dyes (gentian violet, Janus green),
a result reported previously by Churchland and Russell (219) using
cultured frog pericardial cells. As described in Indirect Effects
(Photosensitization) (below), the result with the dyes probably
involved the generation of toxic photoproducts due to the
interaction of light with the dyes.
Macklin (218) and Kite (220) showed that placing a filter
between the light source and condensor reduces phototoxicity in
cultured plant and animal cells. The filter consisted of a glass
vessel filled with a solution of dye (copper sulphate or copper
acetate) that restricted transmission to wavelengths between 450
and 670 nm (actually 280–670; see ref. 221). In 1922, Goodrich
and Scott (222) found that illumination of embryonic chick heart
cells with a tungsten–halogen lamp was not harmful if the intensity
was kept below 280 foot-candles. In 1958, Frederic (223) showed
that 90 foot-candles was damaging to cells when using violet-blue
light (436 and 511 nm) but not green, yellow or red light (556, 571
and 625 nm). In the presence of Janus green, he noted that even 4
foot-candles was toxic. Curiously, these authors failed to cite the
substantial literature on the toxic effects of light and dyes on other
tissues and organisms. It is unclear whether they were unaware of
this literature or whether they felt that it was so well known that it
did not need to be cited.
Between 1932 and 1934, Kemp and Juul (224) and Mayer and
Schreiber (225) reported that UV rays retard division of cultured
mammalian cells. In 1944, Carlson and Hollaender (226) used
grasshopper neuroblasts to show that the effects of UV rays on cell
division depend upon the cell cycle. Early prophase was the most
sensitive period, resulting in slower division. In 1974, Wang et al.
(227) reported that UVA rays killed cultured mammalian cells,
although they suspected that it was due to toxic photoproducts
induced in the culture medium. Between 1978 and 1980, Parshad,
Sanford and colleagues (228,229) determined that UVA and violet-
blue light had a lethal effect on cultured mammalian cells even
when irradiated in saline. They provided direct evidence of single-
strand DNA breaks and indirect evidence that production of
hydrogen peroxide was involved. Peak and Peak (230) confirmed
these results and demonstrated that DNA–protein crosslinking also
occurs.
Damage to excitable cells. Between 1931 and 1957, many
investigators demonstrated that exposure to UV rays decreases the
excitability of neurons including Audait (231), Hutton-Rudolph
(232), Lu¨thy (233), Booth et al. (234), Boyarsky (235), von Muralt
and Sta¨mpfli (236), Gasteiger (237), Lu¨ ttgau (238) and Pierce and
Giese (156). The absorbance of UV radiation by nerve cells
differed from the action spectrum of the response (i.e. wavelength
dependence). The absorption peak was between 240 and 270 nm,
whereas the peak of the action spectrum was around 310 nm. This
disparity led Booth and his associates to suggest that thiamin may
be involved in the response. Lu¨ttgaus results indicated that UV
rays induce a decrease in membrane sodium permeability,
consistent with the possibility of membrane injury. Chalazonitis
(239) showed that the photodynamic action of dyes on nerve cells
resembled the effect of UV radiation alone, suggesting a common
mechanism.
Blindness. In 1916, Verhoeff and Bell (77) studied the effect of
UV rays (below 305 nm) from an Hg arc lamp on the eyes of
rabbits. They found dose-dependent effects on the conjunctiva,
cornea, iris and lens. At low doses, there was a slight conjunctival
hyperemia but no effect on the other ocular tissues. At medium
doses, haziness of the cornea developed. At high doses, there was
edema and purulent exudation in the cornea and iris. Upon
microscopic examination, the lens capsular epithelium was
swollen, and there was a ring of densely packed cells surrounding
the exposed region. Some changes emerged 24–48 h after
irradiation including shedding of the corneal epithelial cells and
leukocyte infiltration of the damaged areas. There was evidence of
repair after 3–10 days, and by 5 weeks all tissues exhibited marked
recovery. There was no noticeable damage to the retina even with
very intense exposures.
In 1976, Ham et al. (240) exposed the retinae of monkeys to
high-intensity laser lines from eight monochromatic sources
between 442 and 1064 nm. The violet-blue lines, but not the
others, caused histological damage similar to that found in retinae
from patients who gazed voluntarily at the sun for 1 h before
submitting to enucleation for malignant melanoma. Because light
transmission through the lens peaks at 470 nm, they argued that
solar blindness is most likely caused by the shorter wavelengths of
sunlight with possible thermal enhancement induced at longer
wavelengths. Over the next two decades, many investigators would
lend support to their hypothesis that violet-blue light is the primary
cause of solar retinopathy (241).
Indirect effects (Photosensitization). There are reports in the
literature describing enhanced light sensitivity in ancient Egyptian
and Indian cultures caused by injestion of certain fruits and
vegetables. There were, apparently, even attempts to treat various
medical conditions using diet and light (242). Nevertheless, the first
scientific reports for such a relationship were noted by Dammann
(243) in 1883 and by Wedding (244) in 1887. They reported that
animals that ate buckwheat in the sunlight developed bubble-
forming rashes on their skin only in areas lacking pigmentation.
Wedding hypothesized that sunlight caused a chemical reaction
with the buckwheat as it traversed the cutaneous blood vessels in
nonpigmented areas. This caused quite a stir and even the famous
scientist Virchow expressed reservations about this interpretation
(244). Over time, additional experiments supported Weddings
idea, and eventually the scientific community embraced it.
The first kind of supporting evidence came from an unlikely
source. Raab (245) found that Paramecia stained with the
fluorescent dye acridine red were killed when exposed to visible
light. He also showed that animals treated with eosin and exposed
to visible light suffered from edema and necrosis in the irradiated
area. While investigating the cause of the toxicity, he found that
neither the light nor the dye was toxic when given alone.
Furthermore, the dye was nontoxic if exposed to light separately
Photochemistry and Photobiology, 2002, 76(6) 569
and then applied. He concluded that it was the combination of dye
and light that was responsible for the effect.
Between 1900 and 1910, von Tappeiner (Raubsmentor),
Jodlbauer and their colleagues went on to show that this toxic effect
(which they called ‘‘photodynamic sensitization’’) could be pro-
duced using any fluorescent dye and any wavelength (UV or visible)
that excited the dye. This led von Tappeiner (246) to propose that it
was the emitted light that was responsible for the toxicity.
In 1932, Blum (3) reviewed the results of 121 papers related to
this topic, and he concluded that it was not the light but rather some
chemical toxin produced by the interaction of light with the dyes.
This effect, he pointed out, was clearly distinct from the direct
effect of UV rays on cells. Photodynamic actions required a dye
or some other chemical to interact with the light, and the response
was dependent upon the presence of oxygen. The latter was
demonstrated by Straub (247), who hypothesized that the photo-
dynamic effect was due to direct oxidation of cellular con-
stituents. Blum (3) surmised that cellular damage was an indirect
effect caused by photooxidation of the dye, resulting in the
generation of a toxic by-product, probably a peroxide. He also
ventured that the photosensitivity of range animals feeding on
either buckwheat or St. Johns wort was due to the same kind of
photochemical reaction.
In 1910, Hausmann (248) sensitized mice to visible rays by
injecting them with hematoporphyrin, a natural blood-borne
molecule that absorbs violet-blue light. He noticed lympocytosis
especially near the surface muscles and speculated that damage to
the blood vessels was the primary cause of the sensitization. In
1919, Adler (249) showed that visible light stimulated skeletal
muscle if the muscle was sensitized with eosin. In 1928, Earle
(250,251) found that illumination of cultured mammalian cells
(fibroblasts and white blood cells) through a microscope was toxic
if red blood cells were present. He presumed that the red blood
cells produced a toxic by-product when exposed to light. In 1937,
Bu¨ngeler (252) showed that photoactive compounds, which were
not inherently carcinogenic, could enhance the carcinogenicity of
light.
Based upon Raubs observations, von Tappeiner (253) predicted
that the interaction of light with chemicals could be a useful tool in
medicine. To test this idea, von Tappeiner and Jesionek (254) used
topical eosin and light exposure to treat human skin tumors.
Although they reported some success, it would take most of the 20th
century to verify the utility of ‘‘photodynamic therapies’’ (255).
MICROORGANISMS, SUNLIGHT
AND UV RADIATION
Microorganisms are single-celled animals that range in size from
100 lm to less than 1 lm in diameter. Their existence and role as
mediators of infectious diseases were established during the 19th
century. Improvements in microscopy allowed scientists to
visualize their morphology and behavior as well as to investigate
the conditions under which they propagated. It was during this
period that scientists discovered the influence of light on these tiny
creatures. Unlike the narratives for humans and nonhuman animals
described above, the damaging effect of sunlight (and UV rays) on
microorganisms was noticed early on.
Pathological responses
In 1845, Schmarda (256) reported that microorganisms found in
stagnant water displayed different responses to light. Some
searched for it; others fled from it; some grew in it; others were
damaged by it. None lived exclusively in the dark. In 1875,
Lessona (257) observed that marine pteropods and heteropods
avoided sunlight and only approached the ocean surface at night. In
1879, Engelmann (258,259) obtained results that supported
Schmardas observations. He showed that the amoeba Pelomyxa
became immotile upon illumination, whereas the photosynthetic
alga Euglena was attracted to light.
About this time, Downes and Blunt (cited in 260) made one of
the most influential discoveries in all of photobiology. They
noticed that direct sunlight inhibited the growth of microorganisms
in test tubes containing Pasteur solution. Illumination for several
hours resulted in test tubes free of bacteria for several months (if
the tube was subsequently sealed with a sterile cotton plug).
Additional tests revealed that the bactericidal action was dependent
upon the intensity, duration and wavelength of sunlight (violet-blue
being the most effective), as well as on the availability of oxygen.
Over the next 20 years, their results were confirmed and extended
by numerous investigators who employed various types of bacteria,
growth media and light sources.
In 1878, Tyndall (260) was the first to confirm Downes and
Blunts observations, but he suggested that it might be due to
suppression of bacterial growth rather than a killing action. In
1882, Jamieson (260) agreed that sunlight had a bactericidal effect,
but that it was most likely due to temperature elevation of the
medium rather than a direct effect on the bacteria. In 1885,
Duclaux (260) and Arloing (260) demonstrated that sunlight had
a direct killing effect on pure cultures of Tyrothrix scaber and
Bacillus anthracis, respectively. Duclaux noted different sensitiv-
ities to light between strains. In 1887, Roux (260) confirmed that
oxygen was required for the bactericidal effect of sunlight on B.
anthracis and its spores. In 1888, Gaillard (260) found that
sunlight was damaging to many kinds of bacteria and spores but
not to molds or yeast. He agreed that the rate of destruction was
dependent upon the intensity of sunlight, the composition of the
medium and the presence of oxygen.
In 1890, Janowski (260) showed that direct sunlight killed
Bacillus typhosus in either liquid or gelatin medium. In addition,
the effectiveness of sunlight was dependent upon the initial
concentration of bacteria and independent of any effect on the
medium. Koch (261) reported that sunlight killed the tubercle
bacillus. In 1891, Tizzoni and Cattani (262) found that exposing
the tetanus bacillus to 1 month of sunlight eliminated its lethal
effect when injected into rabbits. This result was obtained only
when the irradiation occurred in the presence of air (oxygen).
Dandrieu (263) showed that sunlight had a sterilizing effect on
water, and he recommended using artificial light as a means of
sterilizing drinking water. In 1887, Klebs (264) noted in his
‘General Pathology’’ textbook that bacteria and other micro-
organisms grew best when shielded from light, especially sunlight.
He recommended having bushes removed from pastures suspected
of harboring anthrax because bushes shield the bacillus from
sunlight.
In 1892, Geisler (260) used a prism and heliostat to show that
sunlight and electric lamps were lethal to Bacillus typhosus. Using
quartz test tubes, he demonstrated that UV rays were the most
lethal, although longer wavelengths were damaging at higher
intensities. Buchner (260) developed a very sensitive assay for cell
death that allowed him to detect the killing action of direct sunlight
in as little as 10 min. He ruled out any contribution of infrared rays
by exposing the cultures through 0.5 m of water. This led him to
570 P. E. Hockberger
speculate that sunlight has a natural sterilizing effect on rivers,
streams and lakes.
Between 1893 and 1895, Ward (260) performed a remarkable
series of experiments demonstrating superb technical skill and
ingenuity. Using improved versions of Buchners assay and
Geislers apparatus, he showed that violet-blue and near UV
(UVA) rays were the most damaging part of sunlight on bacteria.
He also noted that pigmented fungi were resistant, consistent with
the notion that pigments serve as protective filters. Finsen (50)
showed that sunlight concentrated by a lens and passed through the
ear of a white rabbit was capable of bactericidal action. In 1896,
Westbrook (265,266) showed that the bactericidal effect of
sunlight was greatest at the surface of cultures, whereas bacterial
growth was facilitated deeper in the medium due to elevated
temperature and decreased oxygen availability.
In 1893, Richardson (267) showed that sunlight had a sterilizing
effect on human urine and that irradiation of urine in the presence of
oxygen resulted in the generation of hydrogen peroxide. DArcy and
Hardy (268) showed that UVA and violet-blue rays from a high-
intensity electric arc lamp stimulated production of an oxidizing
substance in water, possibly ozone. This, they suggested, might
explain the bactericidal action reported by Ward. In 1927, Bedford
(269) showed that UV light stimulated hydrogen peroxide pro-
duction in culture medium. This led him to suggest that the
destructive action of UV light on bacteria is caused by the interaction
of light with photosensitizers in the medium resulting in hydrogen
peroxide production leading to irreparable damage to the bacteria.
Between 1900 and 1904, Bie (270,271) used a carbon arc lamp
and liquid filters to confirm that violet-blue and UV rays were
lethal to bacteria. He also noted that oxygen was not required for
the UV effect (272). In 1901, Strebel (273) showed that UV rays
from cadmium and aluminum arc lamps were more powerful than
sunlight for killing bacteria. Bang (274,275) reported that Bacillus
prodigiosus exhibited different sensitivities to UV rays from metal
arc lamps. He recorded lethality with 340–360 (UVA) and 200–
300 nm (UVC 1UVB), although the latter region was more
effective, and lethality increased at warmer temperatures. In 1903,
Barnard and Morgan (276) used a prism and several types of arc
lamps to confirm that the greatest bactericidal action occurred at
emission lines between 226 and 328 nm (UVC 1UVB).
Between 1904 and 1905, Hertel (260) performed the first
rigorous quantitative assessment of the effects of light on
microorganisms. Using a thermopile and galvanometer, he
demonstrated that UV rays from an arc lamp are several orders
of magnitude more lethal than visible rays. The order of potency
was UVC .UVB .UVA .visible rays. He also observed some
interesting cellular behaviors in response to UV rays including
avoidance, strange locomotory behaviors (circular, screwing and
rotatory motions), cell contractions and death.
Between 1906 and 1907, Thiele and Wolf (277,278) used carbon
and Hg arc lamps to confirm Bies observation that the bactericidal
action of UVB and UVC wavelengths did not require oxygen,
whereas killing by UVA–visible rays did. They also noted that
lethality to the longer wavelengths was more pronounced at higher
temperatures (30–408C). In 1910, Cernovodeanu and Henri
(279,280) argued that the UV action of arc lamps on bacteria
was independent of temperature. In 1914, Henri and Moycho (281)
determined that 280 nm was the most lethal emission line of the arc
lamps, and they calculated that an emission energy of 2 310
5
erg/
cm
2
was needed to kill the bacteria. Henri and Henri (282) showed
that sublethal doses of UV radiation modified the metabolism of B.
anthracis so that, unlike the original bacilli, it was able to obtain
nitrogen from ammonium salts or amino acids as well as grow in
sugar-containing media. This was the first demonstration of the
mutagenic effects of UV rays.
In 1917, Browning and Russ (283) found no germicidal effect of
a tungsten arc lamp with emission lines longer than 300 nm,
although no intensity measurements were reported. Bovie and
Hughes (284) found that a sublethal dose of UV rays at 280 nm
inhibited cell division of Paramecia. They noticed that upon
removal of the irradiation, cell division was often accelerated.
Henri (285) found that egg albumin absorbs rays in the UV region
leading him to suggest that the bactericidal effect of sunlight is
proportional to protoplasmic absorption. Burge (286), however,
killed bacteria with UV rays, extracted their enzymes and found
that the proteolytic enzymes were unharmed.
In 1923, Bayne-Jones and van der Lingen (287) demonstrated
that the absorption spectrum of a bacterial emulsion correlated with
the wavelength-dependence of the bactericidal action between 185
and 350 nm. They found no bactericidal action at wavelengths
longer than 350 nm even at 408C or pH 4.6, conditions that
accelerated killing at shorter wavelengths. Coblentz and Fulton
(288) calculated the total energy needed to kill a single bacterium
was 19 pW from an Hg arc lamp emitting at 170–280 nm. They
demonstrated that continuous and intermittent exposures were
equally effective (reciprocity). Wykoff (289,290) reported that the
energy required to kill bacteria with X-rays was 100 times less than
that required with even the most potent UV rays (i.e. 265 nm). He
calculated that only one in four million absorbed UV photons is
capable of causing cell death.
In 1929, Gates (291–293) measured an action spectrum for the
bactericidal effect induced by an Hg arc lamp. The action spectrum
corresponded to the absorption spectrum of nucleic acids with
a peak response at 265 nm. He proposed that the bactericidal effect
was caused by UV-induced damage to nucleic acids. He also
noticed that cell division was more sensitive to UV rays than to cell
growth. In 1945, Tatum and Beadle (294) used Hg arc lamps to
induce mutations in Neurospora, supporting a direct effect of UV
rays on nucleic acids.
In 1943, Hollaender (295) reported that E. coli were killed with
light of 350–490 nm (UVA 1violet-blue), but it required 10 000–
100 000 times more incident energy than at 265 nm (UVC). The
response at longer wavelengths was also different in that it
displayed a threshold, temperature coefficient (Q
10
) of 2 and
caused retarded growth and other sublethal effects. Jagger and
colleagues (296) confirmed Hollaenders observation that UVA
rays inhibited bacterial growth as well as cell division in the
absence of exogenous sensitizing agents. Webb and Bhorjee (297)
demonstrated that UVA and violet light as low as 5 kJ/m
2
completely inhibited the induction of an enzyme in Escherichia
coli (b-galactosidase).
Webb (15) reviewed the literature showing that UVA rays cause
lethal and mutagenic effects in microorganisms even in the absence
of exogenous photosensitizers. Unlike UVB effects, UVA effects
are oxygen-dependent. In 1980, DAoust and colleagues (298)
showed that flavins are endogenous photosensitizers that underly
the damaging effect of visible light in bacteria. Hartman (299)
reported that irradiation of E. coli with UV rays (300–400 nm)
induced hydrogen peroxide production, a process that probably
involves flavins (300).
In 1960, Beukers and Berends (301) demonstrated that
irradiation of frozen solutions of thymine with UVC resulted in
Photochemistry and Photobiology, 2002, 76(6) 571
the formation of thymine dimers, and this eventually led to the
discovery that dimers could be formed between adjacent
pyrimidines (302). Hanawalt and Setlow (303) showed that DNA
synthesis rate in bacteria recovers after UV exposure. In 1964,
Setlow and Carrier (304) and Pettijohn and Hanawalt (305)
independently found that DNA is spontaneously repaired in
bacteria after UV exposure. This eventually led to the notion of
nucleotide excision repair (306).
In 1949, Kelner (307) found that the survival of bacteria exposed
to UV rays is higher if they are illuminated with visible light
immediately afterwards (called ‘‘photoreactivation’’). This led to
the discovery of the enzyme photolyase, a flavin-based enzyme
activated by violet-blue light that repairs pyrimidine dimers (308).
Studies of DNA repair mechanisms in bacteria have contributed to
unraveling the basis of certain human disease including xeroderma
pigmentosum and Cockayne syndrome (309,310). There is also
emerging evidence that binding of transcription factors to the
promoter regions of genes can inhibit repair and create hotspots for
UV photoproducts (311,312).
Physiological responses
The physiological response of microorganisms to light was first
noticed by Schmarda (mentioned above), but the first rigorous
studies were performed by Engelmann. In 1879, he found that
Euglena was attracted to light (i.e. positively phototaxic) and that
the light sensitivity resided at the base of its flagellum (258,259). In
1883, he demonstrated that phototaxis of other protozoans toward
Euglena was due to light-induced production of oxygen in the
latter (313). In 1888, he showed that photosynthetic (purple)
bacteria congregated in the near infrared region of the spectrum,
i.e. 800–900 nm (314). He inferred that this was a region of
absorption by a pigment with properties similar to chlorophyll (he
called it ‘‘bacteriochlorophyll’’) that was important for the
photosynthetic growth of the bacteria.
In 1888, Loeb (315) proposed that phototaxis of Euglena is due
to differential stimulation of their pigmented eyespots (stigma),
rather than direct activation of the flagellum. In 1911, Mast (316)
reported experiments indicating that phototaxis involves both the
eyespots and the flagellum. In his model, flagellar motion causes
the bacterium to rotate; rotation, in turn, causes alternating
exposure of a photoreceptor adjacent to each eyespot (which
periodically shades the photoreceptors) producing a succession of
on–off responses. The latter allows alignment of the axis of the
bacterium to the light. In 1915, Buder (317) determined that
Euglena oriented toward a light source in the direction of the light
rays, rather than to the light-intensity gradient. Brucker (318)
observed that the threshold for phototaxis in Euglena was raised by
light adaptation. Links (cited in 319) proposed a model for
bacterial phototaxis which hypothesized that light-induced eleva-
tion of intracellular ATP activates the flagellar motor.
In 1902, Beijerinck (320) reported that chromogenic bacteria are
attracted to light. Pieper (319) found that blue-green algae were
attracted to light greater than 575 nm but were negatively
phototaxic to light below 500 nm. Between 500 and 575 nm, he
found that the reaction was positive in dim light and negative in
bright light. In 1919, Metzner (321) showed that nonphotosynthetic
spirilla became phototactic when impregnated with the photo-
senstizing dye eosin. In 1948, Manten (322) proposed that
phototaxis in purple bacteria results from the sudden decrease in
the rate of photosynthesis upon leaving the light. In 1956, Schlegel
(323) showed that purple bacteria, which are normally attracted to
light, are negatively phototaxic if the intensity is too high. In 1959,
Clayton (324) reported that phototaxis of purple bacteria occurs in
the absence of oxygen and carbon dioxide.
In 1955, Zalokar (325) found increased photocarotenogenesis
in Neurospora (fungus) exposed to violet-blue light. Curry and
Gruen (326) demonstrated positive phototropism to violet-blue
light using Phycomyces (fungus). In 1960, Delbru¨ck and
Shropshire (327) showed that the action spectrum for phototro-
pism in Phycomyces corresponded to the absorption spectrum of
flavinoids. Sargent and Briggs (328) demonstrated that violet-blue
light altered the circadian rhythm of Neurospora. Diehn (329)
confirmed Curry and Gruens observation using Euglena.In
1979, Bialcyzyk (330) reported that motile cells of Physarum
(slime mold) avoided violet-blue light. Recently, Selbach and
Kuhlmann (331) found that Chlamydodon (a ciliated bacterium)
is capable of sensing the direction of light and that it is likely
mediated by a photoreceptor excited by UVA and violet-blue
rays.
Most studies of UVA and violet-blue light responses have
implicated carotenoids and flavins as molecular photoreceptors. In
1935–1937, Castle (332) and Bu¨ nning (333) proposed that
carotenes were involved in phototropism in the fruiting bodies of
Phycomyces and Pilobolus (fungi) and in the coleoptiles of the
plant Avena. In 1950, Galston (334) proposed the alternative
‘flavin hypothesis’’ in which riboflavin acts as a photosensitizing
agent in the photooxidation and stimulation of the growth hormone
(auxin) indole acetic acid. Forty years later, Galland (335) reported
that flavins are still regarded as the most common photoreceptors
in blue light responses, although carotenoids and pterins have been
implicated in some cases.
One of the more controversial discoveries is the observation that
cells produce, transmit and perceive ultraweak electromagnetic
radiation (also called ultraweak photon emission, low-level
bioluminescence and bioelectromagnetism). The controversy was
instigated in 1923 by Gurwitsch (336), who reported that dividing
Paramecia emit weak UV rays (luminescence) that are capable of
stimulating cell division in other Paramecia. His results were
supported by Alpatov and Nastjukova (337), who showed that the
low intensity output from a broadband xenon arc lamp (visible and
UV rays) increases the rate of cell division of Paramecia, whereas
high intensities reduce it. Hollaender and Claus (338,339),
however, were unable to obtain a mitogenic effect in bacteria
with either UV or visible light. Using sensitive detection
techniques, Popp (340) and others have measured spontaneous
emission of low-intensity electromagnetic radiation (visible and
UV) from many types of plant and animal cells including
mammalian cells. The significance of these emissions, typically
10–100 photons per second, is still under investigation.
CONCLUSIONS
The discovery of UV radiation and its effects on living organisms
was a gradual process that involved contributions from chemists,
physicists and biologists. When it became clear that UV radiation
is a component of sunlight, there was much interest in whether it
might be responsible for some of the effects of sunlight on living
organisms. The cumulative evidence to date indicates that UV
radiation has both beneficial and harmful effects depending upon
the type of organism, wavelength region (UVA, UVB or UVC) and
irradiation dose (intensity 3duration).
572 P. E. Hockberger
The biological data so far are consistent with the following
general statements. First, high doses of either UVC, UVB or UVA
radiation are harmful to all living organisms in the following order:
UVC .UVB .UVA. In the case of UVC and UVB, the cause is
direct damage to nucleic acids and proteins that can lead to genetic
mutation or cell death. The mechanism underlying UVA damage is
less well understood, but it probably involves the generation of
reactive oxygen molecules that can damage many different
components of cells including nucleic acids and proteins. Second,
low doses of UVA radiation can induce physiological responses in
organisms probably by activating specific genes. The mechanism
underlying gene activation is unclear, and it is uncertain whether
low doses of UVC and UVB radiation can induce similar
responses. Third, many of the physiological and pathological
effects of UVA radiation can be obtained with violet-blue light.
This is most likley due to a common photochemical transduction
process involving flavinoids and carotenoids.
Acknowledgements—I wish to thank Fred Urbach, Thomas Coohill and
an anonymous reviewer for their critical reading of the manuscript as
well as helpful comments and suggestions. I am grateful to the following
individuals for their assistance in finding many of the references: Ron
Simms and Ramune Kubilius (Galter Health Sciences Library, Northwest-
ern University), Stephen Greenberg (National Library of Medicine), Re-
becca Woolbert (John Crerar Library, University of Chicago), Rich
McGowan (Library of the Health Sciences, University of Illinois at
Chicago) and Michelle Carver (Center for Research Libraries, Chicago).
I also wish to thank Dennis Valenzeno for his encouragement, advice
and suggestions regarding the scope and content of this review.
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Photochemistry and Photobiology, 2002, 76(6) 579
... The pressed cake remaining after the oil is removed is a rich source of protein for farm animals (Valko et al., 2005). Mutation is the sudden change in heritable genetic material at the gene or chromosome level (Hockberger, 2002). They may be caused by error during cell division or by exposure to the DNA-damaging agents or mutagens in the environment (Chatterjee and Walker, 2017). ...
... Gamma radiation has been widely applied in medicine and biology in terms of biological effects induced by a counter intuitive switchover from low doses stimulation to high-doses inhibition (Kamala & Sasikala, 1985). Gamma radiation has provided a number of useful mutants and still shows an elevated potential for improving vegetative plants (Hockberger, 2002;Cheng et al., 2015). The mutagenic effects of sodium azide (NaN3) have been documented in previous reports. ...
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... Environmental factors that cause mutations, such as carcinogens and mutagens have been linked to the etiology of cancer because they play a role in the induction and progression of numerous diseases that affect humans including cancer (Tomasetti et al., 2017). Mutagens can be of physical origins such as ultraviolet rays, chemical origins such as reactive oxygen species, or biological origins that can induce mutations, thereby producing different breaks in DNA and the formation of base dimers (Hockberger, 2002). Sodium azide (NaN3) is a chemical mutagen because it is an azide salt that causes plant mutations (Owais and Kleinhofs, 1988). ...
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Tigernut, also known as Cyperus esculentus, is considered high in nutritional and medicinal value. The purpose of this study was to determine the C. esculentus’s antimutagenic activity. The ethanolic and aqueous extracts of the nut were analyzed for chemical constituents, antioxidants, ultraviolet-visible, and gas chromatography-mass spectrometry using standard procedures. The extracts contained a total of 17 major compounds that were docked against human RecQ-like protein 5 (RECQL5) helicase protein. The antimutagenic property of the ethanolic extract in vitro was assessed using the Allium cepa chromosome assay. Onion bulbs were pre-treated with 200 mg/kg of ethanolic extract of C. esculentus for 24 h and then grown in NaN3 (250 μg/L) for 24 h; onion bulbs were also first exposed to NaN3 (250 μg/L) for 24 h before treatment with 100 mg/kg and 200 mg/kg of the ethanolic extract respectively. Standard methods were used to determine the mitotic index and chromosomal aberrations. Results revealed that C. esculentus ethanolic extract contained flavonoids (22.47 mg/g), tannins (0.08 mg/g), alkaloids (19.71 mg/g), glycosides, phenol, and tannin and showed high scavenging activity against 2,2-diphenyl-1-picrylhydrazyland H2O2. Docking with RECQL5 showed good binding energies (ΔG>−7) of five compounds in C. esculentus ethanolic extract. The A. cepa assay results revealed a significant (P<0.05) reduction in chromosomal aberrations and a higher mitotic index in groups treated with the C. esculentus ethanolic extract. The antimutagenic activity of C. esculentus ethanolic extract was attributed to its high levels of phytosterols and phenolic compounds.
... Recent efforts toward engineering lightsensitive dienophiles such as caged cyclopropenes 21 and bicyclononynes 22 have enabled ultraviolet-light-induced tetrazine ligations with relatively modest reaction rates. However, ultraviolet light is toxic to living cells, particularly mammalian cells, which limits applications 23 . The trans-cyclooctenes (TCOs), the fastest reacting dienophiles, and caged click-to-release dienophiles have not yet been shown to be amenable to photocaging 24 . ...
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Bioorthogonal cycloaddition reactions between tetrazines and strained dienophiles are widely used for protein, lipid and glycan labelling because of their extremely rapid kinetics. However, controlling this chemistry in the presence of living mammalian cells with a high degree of spatial and temporal precision remains a challenge. Here we demonstrate a versatile approach to light-activated formation of tetrazines from photocaged dihydrotetrazines. Photouncaging, followed by spontaneous transformation to reactive tetrazine, enables live-cell spatiotemporal control of rapid bioorthogonal cycloaddition with dienophiles such as trans-cyclooctenes. Photocaged dihydrotetrazines are stable in conditions that normally degrade tetrazines, enabling efficient early-stage incorporation of bioorthogonal handles into biomolecules such as peptides. Photocaged dihydrotetrazines allow the use of non-toxic light to trigger tetrazine ligations on living mammalian cells. By tagging reactive phospholipids with fluorophores, we demonstrate modification of HeLa cell membranes with single-cell spatial resolution. Finally, we show that photo-triggered therapy is possible by coupling tetrazine photoactivation with strategies that release prodrugs in response to tetrazine ligation. Developing stimuli-responsive bioorthogonal tetrazine ligations remains highly challenging, but a versatile approach that uses photocaged dihydrotetrazines has now been developed. Photouncaging results in the spontaneous formation of reactive tetrazines that rapidly react with dienophiles such as trans-cyclooctenes. As a demonstration, the method was used for live-cell labelling with single-cell precision and light-triggered drug delivery.
... UV-C radiation, emitted at wavelengths of 200-280 nm along with UV-A (320-400 nm) and UV-B (280-320 nm), is reported to be retained by the ozone layer. The different regions of UV radiation are shown in Figure 1 [17][18][19]. UV-C radiation, because of its high absorption level by the ozone layer, does not penetrate the earth in any appreciable amount. ...
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Amongst the surface treatment technologies to emerge in the last few decades, UV-C radiation surface treatment is widely used in food process industries for the purpose of shelf life elongation, bacterial inactivation, and stimulation. However, the short wave application is highly dose-dependent and induces different properties of the product during exposure. Mechanical properties of the agricultural products and their derivatives represent the key indicator of acceptability by the end-user. This paper surveys the recent findings of the influence of UV-C on the stress response and physiological change concerning the mechanical and textural properties of miscellaneous agricultural products with a specific focus on a potato tuber. This paper also reviewed the hormetic effect of UV-C triggered at a different classification of doses studied so far on the amount of phenolic content, antioxidants, and other chemicals responsible for the stimulation process. The combined technologies with UV-C for product quality improvement are also highlighted. The review work draws the current challenges as well as future perspectives. Moreover, a way forward in the key areas of improvement of UV-C treatment technologies is suggested that can induce a favorable stress, enabling the product to achieve self-defense mechanisms against wound, impact, and mechanical damage.
... Curiosamente, el descubrimiento de la radiación ultravioleta también está asociado a esta experimentación del oscurecimiento de las sales de plata al ser expuestas a la luz solar. En 1801, el físico alemán Johann Wilhelm Ritter descubrió que los rayos invisibles situados justo detrás del extremo violeta del espectro visible eran especialmente efectivos oscureciendo el papel impregnado con cloruro de plata [107]. ...
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*(ENGLISH) This research focuses on the studies and analysis carried out on an album belongs to art collector and oil tycoon Calouste Gulbenkian (1869-1955), that is part of his photographic heritage. The album consists of 116 albumen prints with topics related to photography in Europe, Middle East and the Caucasus in the late nineteenth century. Currently, is preserved in the foundation created after the owner´s death together with its large art collection. This object has never been studied before, so there are no references and documentation about it. That is why has been necessary two complete researches: historical-artistic and scientific-technical studies in order to increase his value, future conservation and cultural use. For the purpose of complement the historical part of the album, based on specific literature and documentation kept in archive, library and owner's museum, other research methods has been carried out. The recreation of the albumen manufacturing process and characterization of a photographs selected by non-destructive analysis or minimally invasive such as optical microscopy and spectroscopic techniques ED-μFRX, ATR-FTIR, μ-Raman and μ-FTIR has been performed. The combination of both studies has been a great contribution to the knowledge, conservation and the value of the object. *(SPANISH) La presente investigación se centra en los estudios y análisis llevados a cabo sobre un álbum de fotografías a la albúmina que forma parte del patrimonio fotográfico del coleccionista de arte y magnate del petróleo Calouste Gulbenkian (1869-1955). El álbum, que consta de 116 fotografías tomadas en las zonas Europa, Medio Oriente y el Cáucaso a finales del siglo XIX, se encuentra en la actualidad custodiado en los Archivos de la Fundación Calouste Gulbenkian. Para investigar la parte histórica se ha revisado la literatura específica acerca de su colección de arte y la documentación conservada en el archivo, biblioteca y museo del coleccionista. Además, se ha realizado la recreación del proceso de manufactura a la albúmina y el estudio científico de una muestra de fotografías mediante análisis no destructivos o mínimamente invasivos como la microscopía óptica y técnicas espectroscópicas complementarias como ED-μFRX, ATR-FTIR, μ-Raman y μ-FTIR. La combinación de estudios y métodos de investigación de diversas disciplinas ha supuesto un gran aporte para el conocimiento, la conservación y la puesta en valor del objeto.
... Dalga boyu 100-400 nm arasında değişen, X ışınlarıyla görünür ışık arasında kalan elektromanyetik radyasyona ultraviyole (UV) adı verilmektedir. İlk defa 1801 yılında X ışınlarının kimyasal maddelere etkileşimi incelenirken Alman fizikçi Ritter tarafından keşfedilmiştir (Hockberger, 2002). UV ışınlar insanlar tarafından çıplak gözle görülemezken, yakın UV böcek, kuş ve balıklar tarafından görünür. ...
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Conference Paper
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Photodermatology
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AlGaN‐based deep ultraviolet light‐emitting diodes (UV LEDs) have gained rapidly growing attention due to their wide applications in water purification, air disinfection, and sensing as well as optical communication. Moreover, deep UV radiation has been verified as one of effective way to inactivate COVID‐19. However, although numerous efforts have been made in deep UV LED chips, the reported highest external quantum efficiency (EQE) of them is 20.3%, which is far lower than that of visible LEDs. The EQE of commercial packaged AlGaN‐based deep UV LEDs is usually lower than 5%, which will cause serious reliability problems as well. Therefore, it is very urgent to improve EQE and reliability of the devices from packaging level. In this review, a systematical summarization about the packaging technologies of AlGaN‐based deep UV LEDs has been analyzed and future prospects have been made as well. Firstly, this work provides a brief overview of the devices and analyzes why the packaging level reduces EQE and reliability in theory. Then, systematically reviews the recent advances in packaging technologies and deep UV micro‐LEDs. Finally, conclusions and outlooks are given as well. This review is of great significance for promoting the development of the packaging technologies for AlGaN‐based deep UV LEDs. The external quantum efficiency of packaged deep ultraviolet light emitting diodes (UV LEDs) is representatively lower than 5%. Decreasing interface loses is a main strategy to improve light extraction efficiency (LEE) and the high transmittance fluoropolymer can sustain high UV energy to enhance reliability. This review systematically summarizes the recent advances in packaging technologies of deep UV LEDs from the point of improving LEE and enhancing reliability.
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Ultraviolet radiation activates the expression of a wide variety of genes, by pathways which differ between the short non-solar ultraviolet C (UVC) wavelengths, which are strongly absorbed by nucleic acids, and the long solar ultraviolet A (UVA, 320-380 nm) wavelengths, which generate active oxygen intermediates. Intermediate solar ultraviolet (UV) wavelengths in the UVB (290-320 nm) range also contain an oxidative component, but more closely resemble UVC in their gene activating properties. Short wavelength UV, in common with other extracellular stimuli including growth factors, activates signal transduction events that involve both stress- and mitogen-activated protein kinase cascades. The extrapolation of the complex modulation of gene expression that ensues to the consequences of natural UV exposure requires careful attention to the details of doses and wavelength employed in the model experiments. Nevertheless, there is evidence that UVB irradiation of skin can activate the expression of proteins including immunomodulating cytokines, ornithine decarboxylase and, to a limited extent, nuclear oncogene products, as well as lead to stabilisation of p53. Non-cytotoxic doses of UVA radiation also lead to the strong activation of several genes which would be expected to have functional relevance in vivo.
Book
This book represents the culmination of over fifteen years of experimental and theoretical studies aimed at the elucidation of the process by which ultraviolet light induces cancer. In so far as possible the subject matter is treated from a quantitative point of view, whether dealing with the effects of ultraviolet light on isolated cells or on more integrated systems including the induction of cancer. A description of the course of carcinogenesis by ultraviolet light is presented, based on experimental data, in which cancer is treated as a growing tissue mass. This constitutes probably the most complete summary of a cancer process formulated up to this time.