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Fluoride- and electromagnetic radiation-induced genotoxicity and impaired melatonin secretion

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Abstract

Rao and Thakur have shown that the antioxidants melatonin and alma (Emblica officinales, Indian gooseberry) are effective, both individually and in combination, against fluoride-induced genotoxicity in human peripheral blood lymphocyte cells, which was first described in humans in 1994. Some animal and human work also suggests that fluoride (F) can impair the defensive response to genotoxicity by being deposited in high concentrations in the pineal gland and, through an enzyme-inhibiting action, reducing the secretion of melatonin, a powerful antioxidant able to eliminate free radicals and protect DNA. In having the capacity to be both genotoxic and impair melatonin secretion, F is similar to electromagnetic radiation, at power line frequencies and above, and both have very low or zero thresholds for causing toxicity. In view of the seriousness of neoplasia, the effect of fluoride on melatonin secretion warrants further research.
Editorial
Fluoride 46(3)104–117
July-September 2013
Fluoride- and electromagnetic radiation-induced genotoxicity
and impaired melatonin secretion
Spittle
104104
FLUORIDE- AND ELECTROMAGNETIC RADIATION-INDUCED
GENOTOXICITY AND IMPAIRED MELATONIN SECRETION
SUMMARY: Rao and Thakur have shown that the antioxidants melatonin and alma
(Emblica officinales, Indian gooseberry) are effective, both individually and in
combination, against fluoride-induced genotoxicity in human peripheral blood
lymphocyte cells, which was first described in humans in 1994. Some animal and
human work also suggests that fluoride (F) can impair the defensive response to
genotoxicity by being deposited in high concentrations in the pineal gland and,
through an enzyme-inhibiting action, reducing the secretion of melatonin, a powerful
antioxidant able to eliminate free radicals and protect DNA. In having the capacity to
be both genotoxic and impair melatonin secretion, F is similar to electromagnetic
radiation, at power line frequencies and above, and both have very low or zero
thresholds for causing toxicity. In view of the seriousness of neoplasia, the effect of
fluoride on melatonin secretion warrants further research.
Keywords: Alma; Electromagnetic radiation and genotoxicity; Electromagnetic radiation and
melatonin; Fluoride and genotoxicity; Fluoride and melatonin; Melatonin; Pineal inhibition by
electromagnetic radiation; Pineal inhibition by fluoride.
In this issue Rao and Thakur (pp. 128-34) show that the antioxidants melatonin
(N-acetyl-5-methoxytryptamine) and alma (Emblica officinales, Indian
gooseberry) are effective, both individually and in combination, against fluoride-
induced genotoxicity in human peripheral blood lymphocyte cells. The study
follows several previous studies1-3 since 2006 on the ameliorative effects of
melatonin on fluoride-induced toxicity from Professor Mandava V Rao’s group at
Gujarat University, Ahmedabad, where the genotoxic effects for fluoride (F) in
drinking water were first described in 1994 by Sheth, Multani, and Chinoy.4
Professor Niloufer Chinoy’s team found increased sister chromatid exchanges
(SCEs) in persons exposed to F in the endemic areas of North Gujaret (F 1.95–2.2
mg/L or ppm) compared to those living in Ahmedabad (F 0.6–1.0 mg/L).
Rao and Thakur note that exposure to radioactive and genotoxic agents may
affect the cell cycle and increase the frequency of SCEs, average generation time,
and population doubling time. They found that F can bind to Ran protein, which is
involved in the arrangement of microtubules and regulates nuclear cytoplasmic
transport during the three phases of the interphase part of the cell cycle: G1 (cells
increase their size), S (DNA replication occurs), and G2 (significant protein
synthesis occurs, mainly for the production of microtubules).5-6 SCEs occur
during DNA replication as cells pass to S phase, and F affects the cell cycle, cell
membrane, and protein leading to an increase in SCE frequency and a decreased
cell cycle proliferative index. Several studies have linked F exposure to neoplasia
including a 2006 report by Bassin, Wypij, Davis, and Mittleman, which found, in
males, an association between F exposure in drinking water during childhood and
the incidence of osteosarcoma before the age of 20.7-12
Rao and Thakur record that melatonin, secreted from the pineal gland, along
with its by-products, is an extremely powerful antioxidant that is able to eliminate
free radicals, such as reactive oxygen species, and has a particular role in
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protecting DNA. Reduced melatonin secretion has been linked to DNA strand
breaks, chromosome aberrations, and impaired immune system competence.13,14
Thus genotoxicity may result from the direct action of a toxic agent or indirectly
through the toxic agent reducing the secretion of the free radical scavenger
melatonin. In addition to the references above indicating a direct toxic action by
F,1-4,6 there is a literature reporting that F may reduce melatonin secretion. Luke
found that prepubescent Mongolian gerbils (Meriones unguiculatus) fed a high-F
diet had significantly lower pineal melatonin production than those fed a low-F
diet, and sexual maturity occurred earlier in the females.15,16 Melatonin activates
cAMP-sensitive gene expression in the pars tuberalis of the anterior pituitary
gland by the sensitization of adenylyl cyclase, thus synchronizing the
suprachiasmatic nucleus of the hypothalamus and clock-controlled genes in the
peripheral tissue which control the onset of puberty.17,18 She noted that the
possibility of a species difference between humans and gerbils did not allow the
extrapolation of the gerbil data to humans but expressed some concern about the
possible implications of the results of the animal studies. She observed that F was
now being introduced to children to protect against dental caries at a much earlier
stage of human development than had ever occurred before. If the resulting
increased plasma-F levels have caused a decline in the levels of circulating
melatonin during early human development, significant physiological
consequences may have already occurred.
Luke found that the range for the pineal F content in eleven human cadaver
pineal glands, from persons aged 72–100 yr, was 14–875 mg/kg with a mean of
296±257 mg/kg (wet weight), higher than that in corresponding muscle, 0.5±0.4
mg/kg (wet weight), and that it was directly correlated to the pineal calcium
content: r=0.73, p<0.2.15,19 The pineal is both a soft and a mineralizing tissue, and
the mean F concentration found in the pineal calcification was equivalent to that in
severely fluorosed bone and more than four times higher than in corresponding
bone ash, i.e., 8,900±7,700 vs. 2,040±1,100 mg/kg, respectively. The calcification
in two of the eleven pineal glands contained extremely high levels of F: 21,800
and 20,500 mg/kg. She considered that pinealocytes may not function normally in
close proximity to high concentrations of F, which might affect the enzymatic
conversion of tryptophan to melatonin or the synthesis of melatonin precursors,
(e.g., serotonin), or other pineal products, (e.g., 5-methoxytryptamine).15,20
Although no studies are available that specifically address the effect of F
exposure on pineal function or melatonin production in humans, two studies
examined the age of onset of menstruation (age of menarche) in girls in fluoridated
areas.17 Schlesinger, Overton, Chase, and Cantwell found that this was 12 yr in
fluoridated Newburgh, New York, (F 1.2 mg/L) compared to 12 yr 5 mo, in
nonfluoridated Kingston (“essentially fluoride-free”).21 The result was not
significant but, as it was a 10-year follow-up, the girls had not been exposed to F
over their entire lives.17 Some had been only exposed to F for only a few years,
e.g., from age 8–9 yr and those girls in Newburgh, who had been exposed to
fluoridated water since birth or before, had not reached menarche by the time of
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the study. In Hungary, Farkas, Fazekas, and Szekeres found no difference in the
menarcheal age of 12.779 yr in naturally-fluoridated Kunszentmárton (F 1.09 mg/
L) and the age 12.79 yr in low-F Kiskunmajsa (F 0.17 mg/L).22 However, the
study showed that more postmenarcheal girls were present at younger ages in the
high-F town than in the low-F town, although the reported median ages were the
same.17 Of those reporting having reached menarche by the time of the study (159
in Kunszentmárton and 270 in Kiskunmajsa), the youngest were 10 yr (1 girl), 11
(2 girls), and 11.5 (6 girls) in Kunszentmárton (8.0% of the total in the 10–11.5 age
groups, 5.7% of all postmenarcheal girls in the high-F town) and 11.5 (5 girls) in
Kiskunmajsa (4.7% of the total in the 10–11.5 age groups, 1.9% of all
postmenarcheal girls in the low-F town). The F in the water in the two Hungarian
towns was present naturally,23 and Sauerheber has noted that natural fluorides
accompanied by Group II cations such as calcium and magnesium have less
chemical activity over a broad range of cation concentrations, even in the absence
of precipitation, compared to when F is accompanied in solution with Group I
metal cations, such as sodium or potassium.24 He notes that sodium fluoride was
added to the public water at Newburgh, NY. Information on the degree of hardness
of the drinking water at Kunszentmárton is not readily available.
It is of interest to compare F, with its capacity to be genotoxic and to reduce
melatonin secretion in animals and possibly humans, with electromagnetic
radiation (EMR).
The late Dr Neil Cherry, Associate Professor in Environmental Health, Lincoln
University, New Zealand, who died on May 31, 2003 at 56 from motor neurone
disease, found that many studies indicate that radiofrequency/microwave (RF/
MW) radiation13,25-42 and extremely low frequency (ELF) fields13,39,43-54 cause
increased DNA strand breakage and chromosome aberrations. This effect has been
reported in cell lines, human blood, animals, and living human beings.
Epidemiological studies have shown the expected increases in cancer, miscarriage,
and reproductive adverse effects.55-62 Three plausible biological mechanisms may
be involved.13 Increased free radical activity and genetic damage to DNA and
chromosomes may occur (i) as a response to the exposure25-62 and (ii) because of
an induced reduction in the free radical scavenger melatonin, for which there is
both animal63,64 and human evidence.65-78 EMR may also (iii) alter cellular
calcium ion homeostasis, which is involved in cell regulation, cell survival and
apoptosis, DNA synthesis, and melatonin regulation.79
A recent 2013 paper by Hillman, Stetzer, Graham, Goeke, Mathson, VanHorn,
and Wilcox examined the EMR effects of ground currents near electrical power
lines on milk production of dairy herds. They found that production was reduced
by eight independent electrical variables including transient voltage and harmonic
distortion.80 In a literature review, with 125 references, they noted that an
electromagnetic field (EMF) proliferates and exacerbates many diseases. These
include neoplasia with leukaemia and cancer of the central nervous system, breast,
ovary, prostate, and testis. Other brain conditions affected are Alzheimer’s disease
and stroke. There also occurred cardiac arrhythmias, including atrial fibrillation,
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and allergies, including asthma. They stated that EMF interrupts communication
between cells, enzyme action, ATP energy transfer, homeostasis, and
neuroendocrine control of the autonomic nervous system. Other effects were
interruption of immune defence, reproduction, and the neuroendocrine response of
the adrenals, thyroid, gonads, and other glands. Hillman et al. referenced that
electrical exposure disturbed melatonin secretion patterns in blood by the pineal
gland. They noted that weak ELF magnetic fields were genotoxic and may
promote DNA damage.
The 29-member BioInitiative Working Group 2012 noted in 2007 that there was
little doubt that ELF caused childhood leukemia.81 They referenced a study which
found that leukemia risks for young boys doubled at only 1.4 mG and above.82
Children with leukemia in recovery had a poorer survival rate if their ELF
exposure at home, or where they were recovering, was between 1 mG and 2 mG in
one study and over 3 mG in another study.81 In the 2012 Supplement to Section 1
of the BioInitiative 2012 report, it is noted that, with 42 epidemiological studies
published to date, power frequency electromagnetic fields (EMF) were among the
most comprehensively studied environmental factors in leukemia. Except for
ionising radiation no other environmental factor was as firmly established to
increase the risk of childhood leukemia. In considering RF EMR, Sage reported
there was a consistent pattern of increased risk of glioma and acoustic neuroma
associated with the use of mobile phones and cordless phones.81,83,84 She also
noted that sperm studies are showing DNA damage, impaired sperm quality,
motility, and viability from cell phones on standby mode and wireless laptop use at
exposures of 0.00034 µW/cm2 to 0.01 µW/cm2.81
The World Health Organization International Agency on Cancer Research
(IRAC) classified both ELF-EMF, in 2001, and RF-EMR, in 2011, as Group 2B
Possible Human Carcinogens.81
Thus both EMR and F share the capacity to be genotoxic and reduce melatonin
secretion. Reduced melatonin secretion is seen to play a central role in the
neoplastic and other diseases associated with EMR exposure.13 Lai and Singh
found that both melatonin and the spin trap compound alpha-phenyl N-tertiary-
butyl nitrone (PBN) could prevent microwave-induced DNA damage suggesting
that free radicals were involved in producing the lesions.39,40 Any reduction in
melatonin secretion might therefore be relevant to the response to cancer and
possibly also in other human diseases such as atherosclerosis and the aging
process.13,14,39,40
Another similarity, between EMR, at power line frequencies, and F, is that for
both the threshold for no-effects has been seen to be zero exposure.
Zero exposure threshold for no-effects for EMR at power line frequencies:
Cherry noted that two studies indicated that the safe ELF exposure level is
zero.13 A report by Savitz et al. of electric utility workers showed a dose-
response relationship in mortality from myocardial infarction and
arrhythmic heart disease with thresholds near zero exposure.86 A second
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study by van Wijingaarden et al. on the incidence of suicide in electric utility
workers also showed a dose-response relationship that had a threshold at
zero exposure.87 These two studies suggesting a zero exposure threshold for
no-effects for EMR are on electric utility workers exposed to US power line
frequency EMR of 60 Hz (hertz, cycles per sec.).
Other studies indicate that for health it is necessary to have exposure to
naturally occurring EMR at approximately 10 Hz.88 The earth’s surface and
the ionosphere form an electrodynamic resonating cavity that produces
micropulsations in the magnetic field at extremely low frequencies, from
about 25 Hz down to 1 every ten sec. Most of the micropulsation energy is
concentrated at approximately 10 Hz. Weaver found that persons shielded
from these natural fields developed irregularities in various circadian
rhythms affecting body temperature, sleep-waking cycles, and urinary
excretion of sodium, potassium, and calcium.88,89 Introducing an
infinitesimal electric field, 0.025 volts/cm, pulsing at 10 Hz dramatically
restored normal patterns to most of the biological measurements.88,89 The
circadian rhythms are dependent on the level of melatonin secretion by the
pineal which is sensitive to the daily cyclic pattern in the earth’s magnetic
field.90 Applying a magnetic field of 0.5 G (gauss) or less, oriented so as to
add to or subtract from the earth’s normal field, will increase or decrease
production of pineal melatonin and serotonin.88
Zero exposure threshold for no-effects for F:
Spittle found that there was no threshold for F neurotoxicity in drinking
water, and that the only assuredly safe level is zero.91 Similarly, after
reviewing the 2006 United States National Research Council report,
Fluoride in drinking water: a scientific review of EPA’s standards, Carton
found that the amount of fluoride necessary to cause the adverse health
effects of moderate dental fluorosis, stage I skeletal fluorosis, decreased
thyroid function, and detrimental effects on the brain, in susceptible
members of the population was at or below the dose received from the
current levels of fluoride recommended for water fluoridation.92 He
recommended that the Maximum Contaminant Level Goal (MCLG) for
fluoride in drinking water should be zero.
In addition, safety standards, based on studies showing evidence of harm, have
been made for both EMR and F.
Evidence-based safety standards for EMR:
Cherry recommended in 2000 an outdoor public exposure limit at the
boundary of properties for RF/MW radiation of 0.1 µW/cm2 (microwatts per
square centimetre).13 This level, which reduces the health risk from outside
to less than that associated with using a computer or being in a kitchen with
a microwave oven on, has been adopted in Salzburg, Austria,13,80 and
Plenum Leganés, Spain.93 It was endorsed by the BioInitiative Working
Group in 2007 in their 1479-page report. They noted, “A precautionary limit
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of 0.1µW/cm2 (which is also 0.614 volts per meter) should be adopted for
outdoor, cumulative RF exposure. This reflects the current RF science and
prudent public health response that would reasonably be set for pulsed RF
(ambient) exposures where people live, work and go to school. This level of
RF is experienced as whole-body exposure, and can be a chronic exposure
where there is wireless coverage present for voice and data transmission for
cell phones, pagers, and PDAs [personal digital or data assistants] and other
sources of radiofrequency radiation. Some studies and many anecdotal
reports on ill health have been reported at lower levels than this; however for
the present time, it could prevent some of the most disproportionate burdens
placed on the public nearest to such installations. Although this RF target
level does not preclude further rollout of Wi-Fi technologies, we also
recommend that wired alternatives to Wi-Fi be implemented, particularly in
schools and libraries so that children are not subjected to elevated RF levels
until more is understood about possible health impacts. This
recommendation should be seen as an interim precautionary limit that is
intended to guide preventative actions; and more conservative limits may be
needed in the future.” (Wi-Fi is a popular technology that allows an
electronic device, such as a personal computer, video-game console,
smartphone, digital camera, tablet, or digital audio player, to connect to the
internet wirelessly using radio waves, via a wireless network access point or
hotspot.)
For ELF EMR, the Group’s 2007 conclusion was: “While new ELF limits
are being developed and implemented a reasonable approach would be a 1
mG [milligauss] (0.1 µT) [microtesla, 1 µT = 10 mG] planning limit for
habitable space adjacent to all new or upgraded power lines and a 2 mG (0.2
µT) limit for all other new construction. It is also recommended that a 1 mG
(0.1 µT) limit be established for existing habitable space for children and/or
women who are pregnant.”81
In a 2012 Supplement to the BioInitiative 2012 report it was noted that on
a precautionary public health basis, a reduction from the BioInitiative 2007
recommendation of 0.1 µW/cm2 for cumulative outdoor radiofrequency
radiation (RFR) down to something three orders of magnitude lower (in the
low nW (nanowatt)/cm2 range) was justified.81 A scientific benchmark of
0.003 µW/cm2 or 3 nW/cm2 for the lowest observed effect level (LOEL) for
RFR was based on mobile phone base station-level studies. Applying a ten-
fold reduction to compensate for the lack of long-term exposure (to provide
a safety buffer for chronic exposure, if needed) or for children as a sensitive
subpopulation yielded a 0.0003–0.0006 µW/cm2 or 0.3–0.6 nW/cm2. It was
noted that these levels might need to change in the future as new and better
studies were completed which might lower or raises the current observed
“effects levels.”81
Despite the evidence-based Salzburg Resolution on Mobile
Telecommunication Base Stations of 0.1 µW/cm2 for RF EMR having been
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made 13 years ago in 2000 at the International Conference on Cell Tower
Siting Linking Science and Public Health at Salzburg, Austria,81,94 there is
still a wide variation in the current international limits, e.g., Salzburg,
Austria: 0.1 µW/cm2; Bulgaria, Hungary, Russia, Switzerland: 2–10 µW/
cm2; PR China: 7–10 µW/cm2; Italy: 10 µW/cm2; Australia: 200 µW/cm2;
Canada, Japan, Germany, New Zealand, USA: 200–1000 µW/cm2, and
United Kingdom: 1,000–10,000 µW/cm2.95 In 2007 the current public
safety standards were 1,000–10,000 or more times higher than levels now
commonly reported in mobile phone base stations to cause bioeffects.81
Using the current figure for bioeffects from mobile phone base stations81 of
0.003 µW/cm2 and the international range of limits of 0.1–10,000 µW/cm2
the current public safety standards are 3–3,000,000 times higher than the
levels causing bioeffects. A million-fold difference in safety levels between
countries currently exists.
Evidence-based safety standards for F:
Spittle derived a threshold value for the occurrence of neurotoxicity of 0.1
mg F/L from a pool of eight studies.88 This matched the prescient
recommendation by Babbitt and Doland in 1939 to the American Water
Works Association that the maximum level of F in drinking water should be
0.1 mg F/L because at least a tenfold margin of safety should be
maintained.96 At present countries vary widely also in their approach to
fluoride levels in drinking water. Water fluoridation is practised in 25
countries: Argentina (19%), Australia (80%), Brazil (41%), Brunei (95%),
Canada (44%), Chile (70%), China in the Special Administrative Region of
Hong Kong (100%), Fiji (36%), Guatemala (13%), Guyana (62%), the Irish
Republic (73%), Israel (70% but due to stop by mid-2014 following a
decision on July 29, 2013, at the Supreme Court sitting as the High Court of
Justice), Libya (22%), Malaysia (75%), New Zealand (62%), Panama
(15%), Papua New Guinea (6%), Peru (2%), the Republic of Korea (South
Korea, 6%), Serbia (3%), Singapore (100%), Spain (11%), the United
Kingdom (11%), the United States (64%) and Vietnam (4%).97 In contrast,
in India, fluoride has been seen to be a poison and that, although slow
acting, it is able to cause a variety of health problems, particularly in the
Indian context, when the diet is deficient in a number of nutrients and the
body is unable to combat fluoride poisoning effects.98 Susheela noted that
promoting fluoridation of dental products in India should be considered as a
crime.98 She considered that the US Environmental Protection Agency
(EPA) set the guideline for fluoride in drinking water in the USA at 4.0 mg/
L for “the strangest reason” and that the WHO guideline of 1.5 mg F/L
being the “desirable” upper limit in drinking water was unsuitable. She
observed that the Republic of Senegal in West Africa had reduced the upper
permissible limit of F in drinking water from 1.5 mg/L to 0.6 mg/L.
The wide variation between countries in standards for both EMR and F may be
related to bureaucratic difficulties in keeping up date with new research findings,
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lobbying by industry for whom lower standards may appear to offer a financial
advantage, and a misplaced trust in official reports by decision making
authorities.99
Many such official reports have been published on the efficacy and safety of
fluoridation.100-102 Similarly, Cherry found that some reports on EMR could not
be trusted.13 In 2000 he said he had no respect for the position on the health effects
of EMR of the World Health Organization (WHO) and the International
Commission on Non-Ionizing Radiation Protection (ICNIRP).13 He noted that
they were being managed and chaired by Dr Michael Repacholi in the mid-1990s
and that very strongly held views that there were only thermal effects came
through consistently and pervasively. Cherry noted that Repacholi had close links
with industry and considered that under Dr Repacholi’s chairmanship the ICNIRP
consistently misquoted and misrepresented the evidence. In Cherry’s opinion, the
ICNIRP rejected all the epidemiological evidence on the grounds that every single
epidemiological study occurred with mean exposure levels orders of magnitude
below their thermally-based standard. Cherry considered that they were highly
selective by using only a small proportion of the available studies in order to
construct and defend their own case. He stated that they dismissed large, reliable,
and well-defined studies as being ill-defined and unreliable and that they stated
that studies did not show significant increases in central nervous system cancers
even when they did with significant dose-response relationships. During this time,
under Dr Repacholi’s leadership, both the WHO and the ICNIRP maintained the
thermal view despite the large and ever-growing body of scientific research that
firmly and conclusively challenged this.13 In 2012, Sage stated that safety
standards based on heating were irrelevant to protect against EMF
(electromagnetic field)-levels of exposure and that there was an urgent need to
revise EMF exposure standards.81 Research showed that thresholds for effects
were very low and that the safety standards needed to be reduced to limit the
biological responses.81
Oxman, Lavis, and Fretheim noted that the guidelines for developing WHO
guidelines did not seem to be closely followed when WHO developed
recommendations for member states with, for example, systematic reviews and
concise summaries of findings being rarely used.103
Rao and Thakur have demonstrated that genotoxicity can be caused by fluoride
and can be ameliorated by the antioxidants melatonin and alma (Emblica
officinales, Indian gooseberry). Similarly, melatonin has been demonstrated to
prevent genotoxicity from EMR.39,40 Rao and Thakur note that the antioxidant
activities of alma may not be attributed to its ascorbic acid (vitamin C) content
alone but be due also to the presence of polyphenols such as ellagic acid, gallic
acid, and various tannins. The daily use of vegetables and fruits as a source of
antioxidants, rather than taking drugs or tablets containing nutrients, has been
recommended by Susheela.98 She lists the antioxidants as vitamin C, vitamin E,
carotene, glutathione, quercetin, allicin, capasaicin, ellagic acid, gallic acid,
epicatechin, lycopene, glucosinolates, lutein and zeaxanthin. She places alma as a
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source of vitamin C and records that it can be consumed as a vegetable, pickle,
chutney, drink, and fruit juice supplement.
The ability of both F and EMR to cause oxidative stress, generate free radicals,
and produce genotoxicity has resulted in them have similar profiles of toxicity. For
example, the sperm studies showing that EMR can cause DNA damage, impaired
sperm quality, motility, and viability81 parallel the studies finding toxicity from
fluoride.98,104,105 These overlapping effects suggest that not only might sources of
EMR radiation need to be considered as a confounding factor when designing
experiments to assess F toxicity but possible areas to investigate for F toxicity
might be found by considering the findings from the extensive EMR research that
has been documented. Some collaboration between the two fields of research has
already occurred with the Comet assay developed by Singh and
McCoy36,37,39,40,106,107 for the detection of DNA damage from EMR being used
to detect DNA damage from F.108-110
In 2000, it was noted by Cherry that eight animal studies and 15 human studies,
involving both ELF and RF EMR, had been done on the effects of EMR on
melatonin secretion.13 In 2012, Sage wrote that 11 of the 13 published
epidemiologic residential and occupational studies are considered to provide
evidence that high ELF MF (magnetic field) exposure can result in decreased
melatonin production.81 The two negative studies had important deficiencies that
may have biased the results. There is sufficient evidence to conclude that long-
term relatively high ELF MF exposure can result in a decrease in melatonin
production. In addition, new research indicates that ELF MF exposure, in vitro,
can significantly decrease melatonin activity through effects on MT1, an important
melatonin receptor.81
Relatively little work (one animal and two human) has been done on the effects
of F on melatonin secretion. Newborns produce minimal melatonin, melatonin
peaks in early childhood, puberty occurs as melatonin declines, melatonin
continues to decline in middle age, and older people produce negligible amounts
of melatonin.14 Cancer is a chronic disease problem from accumulated genetic cell
damage.13 Latencies for children and soft tissue cancers are as short as a few years
while for most cancers development takes 10–40 yr to develop.13 Cancer rates rise
rapidly with age over 65 yr because of the life-time of accumulated cell damage
and the drastic reduction in melatonin that occurs after puberty.13 Luke found that
the inhibitory effects of F on pineal melatonin synthesis in the male gerbil ceased
sometime after 11½ weeks and allowed the enzymic activity in the gerbil pineal to
increase to normal values by 16 weeks of age.15 It is unknown at present whether
the build up of F in the human pineal to high levels, up to 21,800 mg/kg in
calcified pineal tissue ash, interferes with pinealocyte function resulting in lower
melatonin levels and possibly less ability to repair genotoxic damage from a
variety of aetiological factors leading to raised cancer rates, including for breast
cancer, and higher rates of Alzheimer’s disease.81 There is considerable in vitro
and animal evidence that melatonin protects against Alzheimer’s disease.81
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In view of the effects that reduced melatonin may have, on protection from
Alzheimer’s disease, atherosclerosis, and cancer, as well as the uncertainty about
whether increased fluoride ingestion is lowering the age of the menarche, the area
warrants further research. Rao and Thakur’s study in this issue of Fluoride is
important for both its therapeutic implications and for stimulating further thought
on the wider issues of F-induced genotoxicity and melatonin.
Bruce Spittle
Managing Editor, Fluoride
727 Brighton Road, Ocean View, Dunedin 9035, New Zealand
E-mail: spittle@es.co.nz
REFERENCES
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Chapter
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Differences and similarities between the mutagenicity of microwave radiation and VCM were studied on the lymphocytes of persons occupationally exposed to either of these two clastogens. The results of the micronucleus test and the chromosome aberration assay were compared. Our findings provided evidence that the mutagenicity of both VCM and microwave radiation can be detected with both of these tests. However, we detected both quantitative and qualitative differences between VCM and microwave radiation in the induction of aberrations and micronuclei. VCM causes quantitatively more chromosome damage but less dicentric and ring chromosomes than microwave radiation. Anaphase bridges are constantly present in the cultured lymphocytes of VCM-exposed persons but they are rarely seen in the lymphocytes of persons exposed to microwave radiation. The number of micronuclei per a certain number of aberrations is much higher in persons exposed to VCM than in those exposed to microwave radiation. An attempt was made here to point out the main differences in the clastogenic action of a physical and a chemical agent. Such data can be fundamental for better understanding of the genetic effects which derive from mutal action of chemical and physical clastogens.
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