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Inhibitory Effects of Feeding with Carrots or (
−
)-Falcarinol on
Development of Azoxymethane-Induced Preneoplastic Lesions
in the Rat Colon
MORTEN KOBÆK-LARSEN,*,† LARS P. CHRISTENSEN,‡WERNER VACH,§
JELMERA RITSKES-HOITINGA,†AND KIRSTEN BRANDT|
Biomedical Laboratory, University of Southern Denmark, Winsloewparken 23, DK-5000 Odense C,
Denmark, Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre
Aarslev, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark, Department of Statistics, University of
Southern Denmark, Sdr. Boulevard 23A, DK-5000 Odense C, Denmark, and School of Agriculture,
Food and Rural Development, University of Newcastle upon Tyne, Agriculture Building,
Newcastle upon Tyne NE1 7RU, United Kingdom
The effects of intake of dietary amounts of carrot or corresponding amounts of (-)-(3
R
)-falcarinol
from carrots on development of azoxymethane (AOM)-induced colon preneoplastic lesions were
examined in male BDIX rats. Three groups of eight AOM-treated rats were fed the standard rat feed
Altromin supplemented with either 10% (w/w) freeze-dried carrots with a natural content of 35 µg
falcarinol/g, 10% maize starch to which was added 35 µg falcarinol/g purified from carrots, or 10%
maize starch (control). After 18 weeks, the animals were euthanized and the colon was examined
for tumors and aberrant crypt foci (ACF), which were classified into four size classes. Although the
number of small ACF was unaffected by the feeding treatments, the numbers of lesions as a function
of increasing size class decreased significantly in the rats that received one of the two experimental
treatments, as compared with the control treatment. This indicates that the dietary treatments with
carrot and falcarinol delayed or retarded the development of large ACF and tumors. The present
study provides a new perspective on the known epidemiological associations between high intake of
carrots and reduced incidence of cancers.
KEYWORDS:
Daucus carota
; aberrant crypt foci; (3
R
)-falcarinol; BDIX rats; natural toxicant; colon
carcinogenesis
INTRODUCTION
While it is well-known from epidemiological studies that a
high intake of vegetables and fruits reduces the risk of cancer
(1-4), knowledge is still very limited about which components
in these foods are primarily responsible for this reduction. Highly
bioactive plant secondary metabolites are mostly known for their
toxicities at high concentrations (5). However, one of the many
theories in this field predicts that these compounds could have
cancer-preventing effects at lower concentrations, corresponding
to the levels found naturally in food (6), as it has already been
shown for glucosinolates from Brassica vegetables (7).
Several epidemiological studies imply specifically the intake
of carrots as important for this preventive effect. Many studies
have been based on the hypothesis that the antioxidant β-car-
otene was responsible for this. However, subsequent intervention
studies ruled out this explanation, since supplementation with
β-carotene does not reduce cancer incidence and, in some cases,
even increases the risk for this disease (8-10). Even though
carrots are the major source of β-carotene in the diet in Northern
Europe and North America, they also contain a group of
bioactive polyacetylenes, of which falcarinol (Figure 1) clearly
is the most bioactive of the carrot polyacetylenes (11-14).
In the human diet, carrots are the almost exclusive dietary
source of falcarinol. A recent in vitro study aiming to screen
for potentially health promoting compounds from vegetables
showed that falcarinol could stimulate differentiation of primary
mammalian cells in concentrations between 1 and 50 ng/mL,
while toxic effects were found above 100 ng/mL (11). This
biphasic effect (hormesis) of falcarinol on cell proliferation is
fully in accordance with the hypothesis that most highly bio-
active compounds exhibit hormesis (15). Ingestion of carrot juice
containing 13 µg falcarinol/mL by human volunteers resulted
in a plasma concentration of falcarinol of 2 ng/mL for several
hours (16). This is within the range where the in vitro data
indicate that a potentially beneficial physiological effect would
be expected (11). Earlier studies showed that physiologically
* To whom correspondence should be addressed. Tel: +45 65 50 37
21. Fax: +45 65 90 68 21. E-mail: mkobaek@health.sdu.dk.
†Biomedical Laboratory, University of Southern Denmark.
‡Danish Institute of Agricultural Sciences.
§Department of Statistics, University of Southern Denmark.
|University of Newcastle upon Tyne.
J. Agric. Food Chem.
2005,
53,
1823
−
1827 1823
10.1021/jf048519s CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/05/2005
relevant concentrations of falcarinol had a pronounced cytotoxic
effect on several human tumor cell lines in vitro (12-14).
Carrots and carrot extracts can also reduce the incidence of
hepatomas (17), although only minimal curative effects of fal-
carinol were found when a highly invasive form of brain cancer
in mice was studied (12). A more detailed account of the back-
ground for the present study has recently been described (6).
In the present study, we examined the possible cancer
preventive effects of realistic dietary amounts of carrot or
corresponding amounts of falcarinol from carrots on the
development of azoxymethane (AOM)-induced aberrant crypt
foci (ACF) and tumors in male BDIX rats. ACF are precan-
cerous lesions often used as biomarkers for colon carcinogenesis
(18), and we used the distribution among different size classes
as a measure of the extent of their progress toward actual tumors.
MATERIALS AND METHODS
Animals. Male rats from the BDIX/OrlIco strain with a certified
health report were purchased from IFFA CREDO (L’Abresle, France).
The animals were 8 weeks old at the time of the first injection with
AOM, as described in earlier studies (19). All animals were housed in
groups of two rats in Macrolon type III cages (Scanbur A/S, Køge,
Denmark). AOM-treated animals were housed inside an isolator [Isotec
type 13366 (M50), Harlan, The Netherlands] with negative pressure
(3 mm H2O) in order to protect the personnel and the environment
from this carcinogen and its metabolites. Two weeks after the final
AOM injection, the animals were moved outside the isolator and housed
in the same animal room. Rats that did not receive AOM injections
were housed outside the isolator in the same animal room throughout
the study. The animals were kept under standard laboratory condi-
tions: room temperature, 20-24 °C; relative humidity, 50-60%; and
12 h light/dark cycle (lights on from 6.00 to 18.00 h). The temperature
and relative humidity inside the isolator were not recorded separately.
The bedding consisted of irradiated aspen wood chips (Tapvei, Oy,
Kaavi, Suomi), and the cages were changed twice a week both inside
and outside the isolator. While outside the isolator, the rats were given
environmental enrichment as aspen wood shavings and/or wooden
blocks (Tapvei) twice a week. Animals in the isolator were allowed
free access to acidified tap water (acidified with HCl to pH 3 in order
to reduce bacterial growth) via water bottles, which were changed once
during their 8 week stay in the isolator (full details given in ref 19).
Outside the isolator, the rats had free access to nonacidified water in
water bottles, which were changed once a week. Food was available
ad libitum, both inside and outside the isolator. Fresh food was given
at least once a week on top of the remaining food.
Plant Material. Carrots (cv. Bolero) were grown organically at
Research Centre Aarslev in 2002. Tops and bottoms were removed
from fresh, washed carrots, which were then shredded, freeze-dried
below 50 °C (Danish Freeze-Dry, Kirke Hyllinge, Denmark), and
packed in sealed aluminum foil pouches until use.
Extraction, Isolation, and Quantification of (3R)-(9Z)-Heptadeca-
1,9-diene-4,6-diyne-3-ol [(-)-Falcarinol]. Falcarinol was isolated from
carrots according to the procedure described by Hansen et al. (11) with
a few modifications. Eight kilograms of freeze-dried carrots were
extracted twice with 12 L of ethyl acetate (99.9% HPLC grade, Aldrich-
Chemie, Steinheim, Germany) for 24 h at 8 °C. The combined extracts
were filtered and concentrated in vacuo (35 °C) under dim light. The
extract (26 g) was chromatographed on silica gel, eluting with n-hexane,
n-hexane-ethyl acetate (v/v) (9:1, 4:1, 7:3, 3:2, 1:1, 2:3, 3:7, 1:4),
ethyl acetate, and finally with CH3OH [99.9% high-performance liquid
chromatography (HPLC) grade, Aldrich-Chemie]. Fractions containing
crude falcarinol were further purified by preparative reversed phase
(RP) HPLC on a Develosil ODS-HG-5 (RP-18, 250 mm ×20 mm
i.d., Nomura Chemical Co., Seto, Japan) column using the following
stepwise gradient: CH3OH-H2O (v/v), 40:60, 50:50, 60:40, 70:30,
80:20, and 100:0, yielding 235 mg of (-)-falcarinol (purity of >99%,
as determined by analytical RP-HPLC). Monitoring was performed at
256 nm; flow rate, 6 mL/min. (-)-Falcarinol was obtained as a colorless
oil and identified by optical rotation, UV, mass spectrometry (MS) [gas
chromatography (GC)-MS (EI, 70 eV)], one-dimensional and two-
dimensional NMR (1H and 13C NMR and 1H-1H and 1H-13C
correlation spectroscopy), and the complete spectral data set cor-
responded fully with literature values (20-25). The optical rotation
for the isolated falcarinol was found to be levorotatory ([R]D20 -36.8°,
c0.88, CHCl3), which is consistent with literature values {[R]D-36.6°,
c0.92, CHCl3(24); [R]D-36.93°,c0.77, CHCl3(25)}for the 3R
configuration of falcarinol.
Falcarinol was quantified in carrot samples by analytical RP-HPLC.
Extraction of carrot samples for analytical RP-HPLC analysis was
performed by extracting 10 g of freeze-dried carrots twice with 100
mL of ethyl acetate according to the procedure of Hansen et al. (11).
Analytical RP-HPLC was performed on a Merck D-7000 Hitachi HPLC
system using diode array detection. Separations were performed on a
LiChrospher 100 RP-18 column (particle size 5 µm; 244 mm ×4mm
i.d.; Merck, Darmstadt, Germany) at 35 °C, by gradient elution with
solvent A [CH3OH-H2O-trifluoroacetic acid (TFA; Sigma Chemical
Co., St. Louis, MO) (v/v/v), 95:4.5:0.5], solvent B [H2O-CH3OH-
TFA (v/v/v), 94.5:5.0:0.5], and solvent C [CH3OH-tetrahydrofuran
(99.9% HPLC grade, Sigma Chemical Co.) (v/v), 50:50]. Elution
profile: 0 min 26% B and 19% C, 20 min 11% B and 19% C, 21-26
min 0% B and 0% C, 29 min 40% B and 0% C and 39 min 40% B and
0% C. All changes in the programmed gradient were linear; flow, 1.0
mL/min. The HPLC samples were cooled to 10 °C in the autosampler,
and 20 µL of sample was injected. Mobile phases were degassed with
ultrasound for 20 min before use. Falcarinol eluted at 26 min and had
the following UV-maxima: λmax 229, 243, 256 nm. Falcarinol was
identified by peak addition of an authentic standard and quantified in
carrot extract samples using falcarinol as external standard. The validity
of the HPLC method was checked with regard to accuracy, linearity,
and precision.
Rat Diet. Before the main experiment, four male BDIX rats were
given free access to both a standard rat feed (Altromin) and freeze-
dried carrots. The consumption of each type of feed was recorded daily,
and after a run-in period of 14 days, the voluntary intake of freeze-
dried carrots stabilized around 10-20% of the daily total feed intake.
For the main experiment, the standard rat feed (Altromin 1234, Chr.
Petersen Inc., Denmark) was pulverized before addition of the
supplementary materials, to ensure that the rats did not select one
component at the expense of another. Diet group 1 contained standard
rat feed supplemented with 10% pulverized freeze-dried carrots
containing 35 µg falcarinol/g; diet group 2 contained standard rat feed
supplemented with 10% maize starch and purified falcarinol corre-
sponding to 10% carrots; and diet group 3 (control group) contained
standard rat feed supplemented with 10% maize starch. Because the
isolated falcarinol for diet group 2 was applied to the diet in the form
of an ethanol solution, the diets for the two other groups were also
treated with the same amount of ethanol. Each time, portions of 20 kg
diet were prepared for each of the three groups and2Lof96%ethanol
or ethanol solution was applied to the diets using an atomizer, after
which the portion was allowed to dry at room temperature for
approximately1hindarkness before being packed in sealed aluminum
foil pouches. The Altromin and freeze-dried carrots were stored at -20
°C before preparations. The prepared diets were stored at room
temperature, mixed well before use, and used for approximately 1 month
before new diets were prepared. The content of falcarinol in the rat
diets (groups 1 and 2) was measured by analytical HPLC before use
and at approximately monthly intervals throughout the experiment. No
significant differences in the content of falcarinol in either diet were
observed during the experiment.
Design of the Rat Feeding Experiments. A total of 30 rats were
divided into three groups that received different diets, starting 10 days
before the first AOM injection. AOM purchased from Sigma Chemical
Co. was diluted with sterile 0.9% NaCl to a concentration of 5 mg/mL
at the Central Pharmacy of the Odense University Hospital (Odense,
Figure 1.
Chemical structure of (3
R
)-(9
Z
)-heptadeca-1,9-diene-4,6-diyne-
3-ol [(
−
)-falcarinol] isolated from carrots and tested in the present study.
1824
J. Agric. Food Chem.,
Vol. 53, No. 5, 2005 Kobæk-Larsen et al.
Denmark). The AOM solution was stored for about1hatroom
temperature before being injected. Eight of the 10 animals in each
treatment group were given weekly subcutaneous (s.c.) injections of
freshly prepared AOM at a dose of 15 mg/kg body weight for a period
of 2 ×2 weeks separated by a 1 week break (19). The range of the
injection volume used was 0.4 mL at the start and 1.0 mL at the end
of the AOM treatments. Two rats in each treatment group were injected
with a volume of sterile 0.9% NaCl related to the body weight.
Autopsy Procedures. The rats were euthanized after 18 weeks, when
the first symptoms of cancer (blood in stools) were observed in a few
animals, and autopsied to examine for macroscopic alterations. The
animals were killed in 100% CO2, after they had been anaesthetized
(duration max, 30 min) s.c. with a mixture of 0.3 mL of Hypnorm/kg
rat (0.095 mg/kg fentanyl citrate and 3 mg/kg fluanisone, JANSSEN
Animal Health, Beerse, Belgium) and 0.675 mL Dormicum/kg rat
(3.375 mg/kg midazolam, Dumex-Alpharma, Oslo, Norway). Im-
mediately after death, selected organs were fixed in 4% phosphate-
buffered formaldehyde, pH 7.4, for later histopathological examination.
The total length of the intestine was measured, and it was then cut
longitudinally, rinsed in 0.9% NaCl solution, cut into two equally sized
pieces, and pinned on a cork slab. Before fixation, the large intestine
was evaluated for macroscopic neoplasms, where diameter and location
in the intestine were registered.
Identification and Quantification of Tumors and ACF. After
fixation of the large intestine, Giemsa stain [6 mL of stock solution
(The Central Pharmacy at the Odense University Hospital) in 50 mL
of phosphate-buffered saline (PBS), pH 7.2, for 15 min] was used to
visualize the ACF, and excess stain was rinsed off with PBS. The tissue
was placed with the luminal side up in a Petri dish with enough PBS
to cover the tissue. The total numbers of ACF and tumors for each
section of the large intestinal were counted independently by two
persons, blinded to treatment modality, by using a stereomicroscope
at 40×magnification. The aberrant crypts were distinguished by their
increased size and thicker and deeply stained epithelial lining as
compared with normal crypts. An ACF may consist of one to several
crypts, and in the present study, the ACF were classified as small (1-3
crypts), medium (4-6 crypts), or large (more than seven crypts), while
neoplasms larger than 1 mm in diameter were classified as tumors.
Within each class of lesions, the variation coefficient of the single counts
between the two persons was less than 10%. The counts of the two
persons were averaged.
The tumors were fixed in 4% (v/v) formaldehyde buffered with 0.075
M sodium phosphate (pH 7) and embedded in paraffin. The tissues
were cut into 5 µm sections and were stained with haematoxylin and
eosin. Additional sections were cut until characterization of the
neoplasm was certain.
Statistical Analysis. The counts of the four different size classes of
(pre)neoplastic lesions were normalized in the carrot and falcarinol
treatment groups by dividing with the class specific mean count in the
control group. The four size classes were scored from one to four with
increasing lesion size. The effect of the class on the normalized counts
in the two treatment groups (carrot and falcarinol) was assessed by a
regression model using the size class score and the treatment group as
covariates. The correlation among the four size classes of ACF/tumors
within each individual rat has been taken into account in this analysis
by using robust variance estimates.
RESULTS
Although both (+)- and (-)-falcarinol have been isolated
from different plants and appear to occur regularly in plants of
the Araliaceae (12,14,25) and Apiaceae (11,21,23,26), the
optical rotation of falcarinol, and hence the absolute configu-
ration, when isolated from plants has often not been determined.
To the best of our knowledge, the absolute configuration of
falcarinol in carrots has not been determined. Falcarinol was
isolated from carrots by preparative HPLC and identified by
spectroscopic means to be levorotatory falcarinol (see Materials
and Methods). Thus, (-)-falcarinol (Figure 1) tested in the
present study on rats on development of AOM-induced colon
preneoplastic lesions possesses the 3Rconfiguration (24,25).
Animal weight gain was identical in all treatments (data not
shown), and no mortality, signs of distress, or disease nor gross
abnormalities were observed. The histopathological aspects of
the model using the same experimental design as the control
treatment have been reported previously (19). Neither tumors
nor ACF were observed in the two animals per dietary treatment
that were injected with 0.9% NaCl solution (data not shown).
The numbers of each size class of ACF and tumors found
are presented in Table 1. In every dietary treatment, while the
numbers of individual lesions decreased very much with
increasing size of the lesion, each size class still represented a
comparable amount of tissue with aberrant growth pattern. For
example, a tumor typically contained the same amount of tissue
as 50-200 small ACF.
All tumors identified macroscopically were subsequently
identified by histological examination as either adenomas or
carcinomas, with an approximately equal number of each type
in each treatment group (data not shown). All of the carcinomas
were restricted to invading the submucosa.
The number of animals was too small to determine whether
the treatments resulted in differences in the numbers of each of
the various lesion types found or in the sums of all types (Table
1). However, the carrot and falcarinol treatments showed a
significant (P)0.028) tendency to reduced numbers of (pre)-
cancerous lesions with an increasing size of lesions (Figure
2), from no difference relative to control for the smallest ACF,
to a one-third reduction for the fully developed tumors.
DISCUSSION
The relation between lesion size and treatment effect corre-
sponds to the trend expected if the bioactive compound is
capable of reducing the growth of precancerous lesions, under
conditions where the preventive effect is not sufficient to prevent
the initial proliferation (which takes place during the actual
period of challenge with the carcinogen). The observed results
could either be due to a decreased growth rate or survival of
the individual tumor precursor cells (cytotoxicity), to a decrease
in the rate of progression through the stages of carcinogenesis,
or to enhancement of one or more of the rats’ relevant immune
system components. Earlier studies of falcarinol, primarily in
vitro studies of its potential use as a drug, have already shown
effects corresponding to each of these mechanisms (5,27),
although their relative relevance in vivo is still unknown.
Our results thus indicate that consumption of carrot led to a
reduced risk of colorectal cancer in this rat model, which is in
line with the epidemiological data indicating that carrot
consumption provides a protective effect on the development
of cancers. They also show that the effect of falcarinol alone
was of the same magnitude as that of the entire carrots (Figure
Table 1.
Numbers of (Pre)Neoplastic Lesions of Different Sizes in
Colons of Rats Fed with Different Supplements; 10% Added to Their
Respective Diets, Results Expressed as Means
±
Standard Deviations
treatment (supplement used,
10% mixed in Altromin diet)
small
a
(1
−
3
crypts)
medium
a
(4
−
6
crypts) large
a
(>7 crypts)
tumors
a
(
g
1mm
diameter)
freeze-dried carrots containing
35
µ
g falcarinol/g 83
±
28 48
±
19 13
±
8 0.9
±
1.0
maize starch where 35
µ
g
falcarinol/g was added 101
±
43 59
±
35 18
±
12 0.8
±
0.7
maize starch (control) 98
±
17 67
±
16 21
±
9 1.4
±
1.1
a
None of the differences between the three diets were significant when analyzed
within one size class or on summations of total numbers across size classes.
Anticancer Effect of Carrots and Falcarinol
J. Agric. Food Chem.,
Vol. 53, No. 5, 2005 1825
2), which supports the hypothesis that falcarinol is an active
protective substance in carrots. Falcarindiol, which is the
quantitatively predominant polyacetylene in carrots (20), has
also been shown to possess cytotoxic (12,28) and antimutagenic
activity in vitro (29), although it appears to be much less
bioactive than falcarinol (11-14). The bioactivity of falcarin-
diol-3-acetate a further polyacetylene in carrots (20) has so far
not been investigated. The possible mode of action of falcarinol
may be related to its hydrophobicity and its ability to form an
extremely stable carbocation with the loss of water, thereby
acting as a very reactive alkylating agent toward proteins and
other biomolecules (30). This may also explain the highly
allergenic properties of falcarinol (30). A similar mode of action
may be possible for falcarindiol and falcarindiol-3-acetate, al-
though the possibility to generate two active centers for nucleo-
philic attack reduces the lipophilic character of these compounds
and hence their reactivity, in accordance with the observed
nonallergenic properties of falcarindiol (30). So the physiological
effects of falcarindiol and falcarindiol-3-acetate are expected
to be qualitatively similar but quantitatively less than those
found for falcarinol, and furthermore, they may even interact
with falcarinol in an antagonistic manner thereby affecting its
effectiveness. This could explain the possible, although not
significant, differences in the effect and the trend observed
between the treatments with falcarinol and the carrot diet
(Figure 1). Other relevant bioactive compounds in carrots that
have been considered in this context, but about which even less
information is available (6), are isocoumarins such as 6-meth-
oxymellein and a large number of mono- and sesquiterpenes.
As far as we know, these are the first results directly
indicating falcarinol as the primary cancer protective substance
from carrots. As a natural pesticide, falcarinol is best known
for its toxic properties, which are observed at high concentra-
tions, and falcarinol is listed as a toxicant in the Nettox database
(5). It is possible that falcarinol could be beneficial and act as
a cancer preventive substance in the relatively low amounts
found in food, even though it is harmful at high intake levels,
just as it has been shown for other highly bioactive food
components, such as ethanol (4).
To confirm the tendencies presented here in future studies,
higher numbers of animals and/or other models are needed. A
power calculation based on the reported data shows that to obtain
a 90% power for each of the medium and large ACFs, 25
animals per treatment group would be needed. For tumors, the
corresponding number would be 3-4 times higher, due to the
small number of tumors per animal.
The amount of carrot in the diet was chosen to correspond
to the voluntary intake when rats were given free choice between
freeze-dried carrots and Altromin. This ensured that the results
would be physiologically relevant, an issue that is particularly
important when studying food components. Imposing a nutri-
tionally deficient diet could by itself inhibit the development
of cancer (31), but because rats are known to be able to
efficiently detect and avoid nutritionally deficient diets (32),
the described procedure ensured that the carrot treatment was
nutritionally adequate. Still, if the use of starch as a substitute
for carrot in the feed for the other treatments caused so large a
difference in the nutritional value between treatments that the
formation of (pre)neoplastic lesions was affected, it would have
inhibited carcinogenesis in the starch-fed rats. This implies that
in our study we might be underestimating the difference between
the positive control (carrot) treatment and the negative control
(starch) treatment, so we have to regard the observed protective
effect as a minimum estimate. Ten percent of the dry weight of
the daily food intake corresponds to a daily human consumption
of 400-600 g fresh weight of carrot. This is the intake level of
fruit and vegetables recommended by many official agencies
responsible for food safety and quality, to decrease the risk of
cancer and other diseases (3).
The presence of equally high numbers of small ACF in all
treatments could be due to a saturation effect: that the intensive
AOM treatment might have induced the maximal number of
preneoplasms that are able to develop in this system, irrespective
of possible differences in susceptibility related to the feed
treatments. If this has been the case, reduction of the amounts
of AOM used in similar future studies may facilitate quantifica-
tion of effects of treatments on the total number of ACF formed.
If future studies confirm the present results, both in terms of
protection against cancer and absence of indications of toxicity,
it would indicate that the moderately increased falcarinol content
in food could reduce the risk of cancer. The present experiment
together with the experiments leading to it (6) thus highlights
Figure 2.
Effect of treatments with carrot or falcarinol on the average numbers per animal of four types of (pre)cancerous lesions in rat colons, each
size class representing increasingly advanced steps on the progression toward cancer. The size of ACF was measured as the number of crypts found
on a corresponding area of normal colon tissue. The smallest tumors correspond to an ACF size of approximately 20. The trend for reduced relative
numbers with increasing size of lesion was significant at
P
)
0.028.
1826
J. Agric. Food Chem.,
Vol. 53, No. 5, 2005 Kobæk-Larsen et al.
the need to include the many overlooked bioactive food
compounds such as falcarinol in ongoing and planned research
on improvement of food safety and quality, including basic
studies on the functioning of human cells during normal and
abnormal development.
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Received for review September 6, 2004. Revised manuscript received
December 20, 2004. Accepted December 22, 2004. The support of the
Danish Research Council for Agricultural and Veterinary Research,
Danish Food Technology Initiative (FØTEK 3) Grant 2011-00-0040,
and of the Development Centre Aarslev are gratefully acknowledged.
JF048519S
Anticancer Effect of Carrots and Falcarinol
J. Agric. Food Chem.,
Vol. 53, No. 5, 2005 1827
