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U.S. Department of Agriculture,,3 Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203-9034 and * Department of Pharmacology, Toxicology and Internal Medicine, University of Louisville, School of Medicine, Louisville, KY 40292
2To whom correspondence and reprint requests should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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500 µg/g);
or 5) 1.0 µg Se/g diet as selenized
broccoli. In Experiment 2, rats (n = 80) were
allotted randomly to the same basal diet supplemented with the
following: 1) no added Se; 2) 2.0
µg Se/g diet as selenite; 3) 2.0
µg Se/g diet as selenite + low Se broccoli; and
4) 2.0 µg Se/g diet as selenized
broccoli. Rats were fed the diets for 2 wk and injected with a chemical
carcinogen (3,2 dimethyl 4-amino biphenyl or dimethyl-hydrazine in
Experiment 1 or dimethyl hydrazine in Experiment 2; 2 rats/treatment
were used as vehicle controls). Supranutritional amounts of Se supplied
as high Se broccoli significantly decreased (P < 0.05) the incidence of aberrant crypts (AC) and aberrant crypt foci
(ACF; preneoplastic lesions indicative of colon cancer) compared with
other dietary treatments. Diets were controlled for the presence or
absence of broccoli and for the total amount of Se. The reduction in AC
and ACF was a function of Se in high Se broccoli and not a result of
broccoli alone or Se alone. Adequate dietary Se supplied as high Se
broccoli did not accumulate in tissues or increase glutathione
peroxidase activity as well as other forms and amounts of Se. Thus, Se
from high Se broccoli may be metabolized in a manner that diverts much
of the Se into a pool that provides protection against colon
cancer.
KEY WORDS: • selenium • broccoli • colon cancer • selenoprotein • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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). About 130,000
people in the United States were diagnosed with colon cancer in 1999
(American Cancer Society 1999
). Diet is the single
greatest contributor to human cancer, including colon cancer, and may
be associated with 35–70% of the incidence of the disease
(Doll and Petro 1981
). Although various carcinogens are
present in foods, their effects are minor compared with dietary
components that inhibit the cancer process (Doll and Petro 1981
).
Selenium (Se), an essential trace nutrient, has been reported to
improve immune function in animals (Beck et al. 1995a
and 1995b
), enhance neuropsychological function in humans
(Finley and Penland 1998
) and ameliorate specific
disease conditions in humans and animals (Levander 1986
). More recently, convincing evidence has been
presented that consumption of Se in amounts up of 3–5 times the
recommended dietary allowance
(RDA;4
70 µg/d for men and 55 µg/d women)
(National Research Council 1989
) may prevent certain
cancers including colon cancer. Clark et al. (1996)
supplemented human subjects in the Southeastern USA for 10 y with
a placebo or 200 µg of Se/d supplied as high Se yeast.
Total cancer incidence and mortality were significantly reduced by Se
supplementation, with specific reductions of relative risk for lung,
prostate and colorectal cancer.
The health benefits of Se, including cancer protection, have prompted
an interest in increasing Se intakes beyond the U.S. RDA, but limited
choices exist at present for Se supplementation; the most characterized
supplement is the high Se yeast that was used by Clark et al. (1996)
. However, Se also is toxic at intake levels only 5- to
10-fold above supranutritional amounts (Levander 1986
), and there is a possibility that supplement
abuse, and the resulting increased body burdens of Se, may predispose
individuals toward toxicity. In addition, the American Dietetic
Association recommends that, whenever possible, people should consume
the nutrients they need as foods and not as supplements (Hunt 1996
). Therefore, food forms of Se may be preferred over
dietary supplements.
Recommending increased intakes of Se through food is complicated by the
variability of Se concentrations in foods. Different brand names of the
same food product had an almost 10-fold variation in Se content
(Finley et al. 1996
), probably reflecting different
geographical origins of the agricultural commodities used to make the
product.
Similarly, the chemical form of Se in foods is variable. Wheat and meat
are the most important sources of Se in the North American diet
(Holden et al. 1991
), and both sources contain large
amounts of Se as selenomethionine (SeMet). Selenomethionine is
excellent for increasing the Se concentration of tissues
(Whanger and Butler 1988
), but it is relatively
ineffective for suppression of carcinogenesis (Feng et al. 1999
, Ip and Ganther 1996
). The mechanism for Se
inhibition of carcinogenesis is unclear. It is probably not associated
with tissue Se accumulation or selenoprotein production, but may be
associated with the monomethylated form of Se in the excretory pathway
(Vadhanavikit et al. 1993
). Consequently, forms of Se
that are metabolized preferentially to methyl selenol may provide
superior cancer protection (Vadhanavikit et al. 1993
).
Se-methyl selenocysteine (SeMSC) is easily converted to methyl selenol
and is a primary form of Se found in broccoli and high Se garlic
(Cai et al. 1995
). Ip and Lisk (1994a
, 1994b)
and 1995
demonstrated that high Se garlic suppresses chemically
induced mammary tumors in animals. Garlic consumption is limited by
personal preference and social concerns, but broccoli consumption does
not have these disadvantages. Consequently, if Se from high Se broccoli
proves to have health benefits similar to those of high Se garlic, then
high Se broccoli may be an ideal food for increasing the Se intake of
humans.
Although colorectal cancer is a form of cancer that was demonstrated by
Clark et al. (1996)
to be suppressed by Se
supplementation, there have been relatively few studies of the
effectiveness of nutritional amounts of Se in suppressing the disease.
This report uses aberrant crypts (AC) and aberrant crypt foci (ACF) as
preneoplastic indicators of colon cancer. Most reports of the
effectiveness of Se in preventing AC and ACF have used synthetic forms
of Se at pharmacologic doses (Reddy et al. 1996
and 1997
); this report concerns the effectiveness of nutritional
and supranutritional doses of Se from broccoli.
The objective of this study was to further our understanding of the metabolism and health benefits of Se from broccoli. Specifically, we desired to test the hypothesis that Se from high Se broccoli is better than other forms of Se for suppression of preneoplastic lesions in the colon. Additionally, we wished to study the regulation and distribution of Se from broccoli, and determine whether alterations in these variables may be associated with its unique health benefits.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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3,2'-Dimethyl-4-aminobiphenyl (DMABP) was purchased from Toronto Research Chemicals (Toronto, Canada). Dimethyl hydrazine (DMH) was purchased from Sigma Chemical (St. Louis, MO). Methylene blue was obtained from Eastman Kodak Company (Rochester, NY).
Production of high Se broccoli.
Broccoli (Emperor Hybrid, Northrup King Lawn and Garden, Chattanooga,
TN) was planted in one-inch flats containing general purpose
growing medium. Seedlings remained in the flats until they developed a
root system (2 wk) and then were transplanted individually into
6.0-L containers. Plants were fertilized with 14–14-14 fertilizer.
Approximately 2 wk before heads began to form, 10 mL of 5.2 mmol/L
sodium selenate solution was added to each plant container. This
solution was added 2 times/wk until the heads became visible; then the
amount of solution was increased to 20 mL 2 times/wk until heads were
fully formed. Fully formed heads were harvested, immediately frozen and
lyophilized. Diets for animal studies used dried powder from the
composited heads. Broccoli produced in this manner averaged 500
µg Se/g dry broccoli powder; low Se broccoli was
obtained from a local grocery store and averaged <1
µg Se/g dry broccoli.
Animals and diets.
All studies were approved by the Animal Care and Use Committee of the
Grand Forks Human Nutrition Research Center, and rats were maintained
in accordance with the NIH guidelines for the care and use of
laboratory animals (NRC 1985
).
F-344 inbred rats (weanling males) were purchased from Charles River Laboratories (Wilmington, MA). Rats were housed individually in hanging wire cages in a room controlled for humidity, temperature and light cycle. Rats were given free access to the food and deionized water.
Two experiments were conducted. Experiment 1 used 45 rats allocated to
five diets in a manner to equalize initial weights. The basal diet has
been described (Davis et al. 1999
) and was a low Se
torula yeast diet supplied by Tek-Lad (Madison, WI) that was
supplemented as follows: low Se broccoli and no added Se (deficient
diet), 0.1 mg Se/kg diet as selenate and low Se broccoli (0.1 selenate
diet), 1.0 mg Se/kg diet as selenate and low Se broccoli (1.0 selenate
diet), 0.1 mg Se/kg diet supplied as high Se broccoli (0.1 broccoli
diet) or 1.0 mg Se/kg Se supplied as high Se broccoli (1.0 broccoli
diet). All diets contained the same amount of broccoli. If the Se
source was not broccoli, or if broccoli that was not as high in Se was
needed, the additional broccoli was added as the low Se variety. Seven
rats in each group were given injections of carcinogen (see below) and
three were injected with vehicle.
Experiment 2 used 80 rats assigned by weight to four diets. The basal diet (same as Experiment 1) was supplemented as follows: no Se and no low Se broccoli (deficient diet); 2.0 mg Se/kg diet as selenite and no low Se broccoli; 2.0 mg Se/kg diet as selenite and low Se broccoli; or 2.0 mg Se/kg diet supplied as high Se broccoli. The last two diets contained equal amounts of broccoli. Eighteen rats in each group were injected with carcinogen (see below) and two were injected with vehicle.
Experimental design.
Rats were assigned to treatments and given access to food and water
immediately upon arrival. Rats were fed their respective diets for 3 wk
and then injected with the carcinogen. The carcinogen used in
Experiment 1 was 3,2'-dimethyl-4-aminobiphenyl (DMABP; 100 mg/kg body)
in a solution of peanut oil. The carcinogen in Experiment 2 was
dimethyl hydrazine (DMH; 25 mg/kg body) in a solution of PBS and 1
mmol/L EDTA. The carcinogen was administered as two subcutaneous
injections on consecutive weeks. Details of the administration have
been described (Feng et al. 1999
). Rats had continuous
access to food during the period of injections.
After the second injection, rats were fed their respective diets for an additional 8 wk. Rats were killed by cardiac puncture after ketamine/xylazine anesthesia. Rat tissues were immediately removed, flash frozen in liquid nitrogen and stored at -70°C.
Aberrant crypt analysis.
The lower bowel was removed, washed in normal saline, fixed and stored
in 70% EtOH until staining and counting of aberrant crypts (AC) and
aberrant crypt foci (ACF). The number of ACF gives the number of sites
of abnormal colonic cells, whereas the number of AC gives the total
number of abnormal cells. The AC and ACF were scored under a dissecting
microscope after staining in 0.1% methylene blue by an operator who
was unaware of the dietary treatments. Detection and counting of AC and
ACF were described previously (Feng et al. 1999
).
Selenium status.
Selenium concentrations in the plasma and liver were determined by
hydride-generation atomic absorption spectrometry according to a
previously published procedure (Finley et al. 1996
).
Samples were prepared for analysis by predigestion in nitric acid and
hydrogen peroxide, followed by high temperature ashing while in the
presence of MgNO3 as an aid to prevent Se volatilization.
Glutathione peroxidase (GSH-Px) enzyme activity was determined by the
coupled enzyme method of Paglia and Valentine (1967)
,
which uses hydrogen peroxide as the substrate.
Glutathione-S-transferase.
The activity of cytosolic glutathione transferase (GST) was determined
spectrophotometrically at 25°C with 1-chloro-2,4-dinitrobenzene as
the substrate according to the method of Habig et al. (1974)
. The reaction mixture contained 100 mmol phosphate
buffer (pH 6.5), 1 mmol glutathione and 1 mmol
1-chloro-2,4-dinitrobenzene/L. The reaction was started by the addition
of cytosol. Protein concentration was determined by the Bio-Rad
protein assay (Hercules, CA).
Statistical analysis.
The effect of dietary treatment on animal weights and indicators of Se status was analyzed by one-way ANOVA. If dietary treatment was significant, then individual means were compared by Tukey’s pairwise contrasts.
Aberrant crypt data were analyzed by nonparametric statistics by using
the generalized linear model procedure (Genmod) in PC/SAS (SAS
Institute, Cary, NC). The incidence of aberrant crypts or
aberrant crypt foci was assumed to follow a Poisson distribution. For
Experiment 1, the independent variables were form and amount of Se. If
the overall effect of dietary treatment was significant, then the
sources of Se were compared by a priori contrasts nested within the
overall design; groups fed Se as selenate (0.1 selenate and 1.0
selenate diets) were compared by 
2 to groups fed high Se
broccoli (0.1 broccoli and 1.0 broccoli diets). For Experiment 2, the
independent variable was dietary treatment, which consisted of the
control group and the 3 treatment groups. If the overall effect of
dietary treatment was significant, then the group fed 2.0
µg Se/g as high Se broccoli was compared by a priori
contrasts (2) to each of the other three treatment
groups.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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Dietary treatments did not affect final rat body weights in either
experiment (Tables 1
and
2
).
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Experiment 1 |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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Selenium concentrations and GSH-Px activities of most organs and
tissues were lowest in rats fed the Se-deficient diet (Table 1)
.
Except for Se-deficient rats, Se concentrations in the muscle and
vesicular gland were not affected by dietary treatment. In the liver,
kidney and brain, apart from the Se-deficient rats, GSH-Px
activity was lowest in rats fed 0.1 mg Se/kg diet as high Se broccoli,
and there were no differences among rats fed 0.1 µg Se/g
diet as selenate, 1 µg Se/g diet as selenate and 1
µg Se/g diet as high Se broccoli.
Se accumulation in erythrocytes, plasma and colon was similar to that of GSH-Px, i.e., rats fed the Se-deficient diet had the lowest tissue Se concentrations and rats fed 0.1 µg Se/g diet as high Se broccoli had significantly lower tissue Se concentrations than rats fed other sources or amounts of Se.
GST activity.
Liver glutathione transferase activity (Table 1)
was significantly
lower (P < 0.03) in rats fed 0.1 µg Se/g
diet as selenate than in those fed the selenium-deficient diet or 1
µg Se/g as selenate. Kidney, muscle and testicular
glutathione transferase activities were unaffected by the dietary
treatments.
Aberrant crypt and aberrant crypt foci abundance.
There was a significant overall effect of diet on the number of AC in
rats in Experiment 1 (P = 0.05). Nonparametric
2 comparisons showed that rats fed diets with
Se as high Se broccoli had significantly fewer AC in the total colon
and rectum than rats fed Se as selenate (P = 0.02;
Fig. 1A
). There also was a trend (P = 0.07) for fewer ACF in
rats fed high Se broccoli compared with those fed selenate (Fig. 1B
). Selenium from broccoli, compared with selenate,
significantly reduced the number of AC and ACF in the descending colon
(arbitrarily defined as the last one third of the colon and the area of
greatest abundance of AC and ACF) (mean; 95% confidence interval: 2.1;
1.4–3.0 and 3.4; 2.6–4.5 for ACF of rats fed broccoli or
selenate, respectively, P = 0.03; 4.3; 2.7–6.9 and
8.6; 6.2–12.1 for AC of rats fed broccoli or selenate, respectively,
P = 0.02).
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Experiment 2 |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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Dietary treatment significantly altered Se status of rats as judged by
differences in plasma and liver Se concentrations (Table 2)
. Selenium
concentrations were lowest in rats fed the Se-deficient diet and
highest in rats fed low Se broccoli and 2 µg Se/g diet as
selenite. The concentration of Se in the liver of rats fed 2
µg Se/g as high Se broccoli was significantly lower than
that in rats fed low Se broccoli and 2 µg Se/g diet as
selenite.
Aberrant crypt and aberrant crypt foci abundance.
There was a significant overall effect of diet on the formation of AC
(P = 0.01; Fig. 2A
) and ACF (P = 0.02; Fig. 2B
) in the total
colon and rectum of rats injected with DMH; 2
comparisons of treatment means showed that rats fed 2 µg
Se/g diet as high Se broccoli had significantly fewer AC (comparison to
0.1 selenite, P = 0.04; comparison to 2 selenite,
P = 0.03; comparison to 2 selenite + low Se broccoli,
P = 0.001) and ACF (comparison to 0.01 selenite,
P = 0.01, comparison to 2 selenite, P = 0.03; comparison to 2 selenite + low Se broccoli, P
= 0.005).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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) stated that the available evidence is sufficient to
recommend increased Se intakes in Great Britain. Another recently
published article (Irion 1999
) hypothesized that high Se
Brassica species may be effective against certain cancers.
These reports demonstrate that the medical community recognizes the
benefits of increased intakes of Se, but they also recognize that the
form of Se that is consumed influences its health benefits. The present
research is the first, to our knowledge, to demonstrate that Se from
high Se broccoli is superior to salt forms of Se for protection against
precancerous lesions in the colon.
Selenium that enters the body may follow one of several metabolic
pathways, and that pathway is determined by the chemical form of the Se
that was ingested. Selenium consumed as a salt is nonenzymatically
reduced to the selenide, which may either incorporate into specific
selenoproteins or be methylated sequentially in the excretory pathway.
Selenium ingested as SeMet may follow the transsulfuration pathway, be
converted to SeCys and then cleaved to produce selenide. However, this
is a complex pathway with many regulatory steps, and a more direct fate
is for SeMet to substitute for methionine and incorporate into proteins
with a methionine requirement (Butler et al. 1989
). High
Se broccoli, however, contains SeMSC (Cai et al. 1995
),
which may be converted quickly to methyl selenol by cleavage of the
Se-methyl group (Foster et al. 1986
). Monomethyl
selenol is considered to be the critical metabolite for protection
against certain cancers (Ip and Ganther 1996
).
In this study, high Se broccoli was more effective than selenate,
selenite or broccoli alone for inhibiting preneoplastic lesions in the
colons of rats administered either DMABP or DMH. In Experiment 1, 1
µg Se/g diet supplied as high Se broccoli significantly
reduced the number of AC in DMABP-treated rats by almost 50%. In
Experiment 2, rats fed 2.0 µg Se/g diet as high Se
broccoli and injected with DMH (DMH is a more potent carcinogen than
DMABP and induces 20-fold more AC and ACF than DMABP) also had
50% the number of AC and ACF as rats fed other diets. Both
experiments controlled for the total amount of broccoli in the diets,
and broccoli alone did not decrease AC or ACF.
The chemical form of Se in broccoli is similar to Se in garlic
(Cai et al. 1995
). Ip and Lisk (1994a
, 1994b
and 1995)
reported previously that high Se garlic reduced the
number of dimethyl benzanthracene–induced mammary tumors in rats.
Thus, this study adds to the increasing evidence that Se in the form
found in garlic and some Brassica species is unique, and
especially beneficial for protection against several different cancers.
Further, the inhibition of carcinogenesis by high Se broccoli and
garlic seems to be a consequence of the uniqueness of Se in those
plants, and not a consequence of the total intake of Se, garlic or
broccoli.
Because different forms of Se undergo different metabolic
transformations, increased anticarcinogenic properties of high Se
broccoli must be a result of metabolism that allows more Se to enter
the cancer-protective pool. The unique metabolism of Se from high
Se garlic and broccoli was reported previously. We fed healthy men
stable isotopes of Se as selenate or hydroponically incorporated into
broccoli (Finley 1999
) and found that Se from broccoli
did not accumulate in the plasma as well as selenate. We also repleted
Se-deficient rats with 0.1 µg Se/g diets supplied as
selenate, selenite, SeMet or high Se broccoli (Finley 1998
) and found that Se from broccoli did not accumulate in
most tissues and organs to the same degree as other forms of Se,
although a few organs accumulated the same amount of Se regardless of
dietary source. Ip and Lisk (1994b)
reported
similar findings with high Se garlic. Rats were fed 3.0 µg
Se/g diet as selenite or high Se garlic, and Se concentrations in
livers and kidneys of rats consuming high Se garlic were 70% those
of rats fed selenite. However, mammary Se concentrations were similar
for high Se garlic and selenite, and muscle Se concentrations were much
higher in the group fed high Se garlic. Studies conducted with
75Se-labeled SeMSC (Foster et al. 1986
) did not give directly comparable results to studies with
high Se garlic and high Se broccoli.
Selenoproteins are primary pools of Se in animals. Consequently, if the
body controls the incorporation of Se into selenoproteins, then it may
control indirectly the amount of Se that enters cancer-suppressive
pathways. In Experiment 1 of this study, rats fed 0.1 µg
Se/g diet as selenate, 1.0 µg Se/g diet as selenate and
1.0 µg Se/g diet as high Se broccoli had similar tissue Se
concentrations and GSH-Px activities. However, consistent with
results from our previous study (Finley 1998
), liver,
testis, brain and vesicular gland GSH-Px activities, and colon and
erythrocyte Se concentrations in rats fed 0.1 µg/g Se as
high Se broccoli were 
50% of the same measures in rats fed
diets supplemented with other forms of Se. The greatest effect of diet
was in GSH-Px activity in the liver; rats fed 0.1 µg
Se/g diet as high Se broccoli had hepatic enzyme activities that were
only 15% of those in rats of the other Se-supplemented groups.
Hepatic GSH-Px is quite labile (Yang et al. 1989
)
and decreases in times of Se deficiency more readily than other
selenoproteins. GSH-Px1 also may act as a Se "buffer" or storage
protein (Sunde 1994
); decreases in the production of
hepatic GSH-Px1 may represent a major diversion of Se into other
pathways. When Se from high Se broccoli was fed at a level
approximating the nutritional requirement, then this diversion
prevented the saturation of GSH-Px activity, a selenoprotein
relatively low in the hierarchy for Se use. However, when high Se
broccoli supplied 2.0 µg Se/g diet, then there was
sufficient Se to maximize GSH-Px activity and protect against
carcinogenesis.
The lack of cancer protection by supranutritional amounts of Se in the
form of a salt (1.0 mg/kg in Experiment 1, and 2.0 mg/kg in Experiment
2) may be a consequence of unique aspects of the experimental design of
this study compared with studies that have found salt forms of Se to be
protective (Feng et al. 1999
, Ip and Lisk 1994b
). Experiment 1 included broccoli in all diets, and it is
possible that broccoli alone resulted in changes of AC and ACF
formation that were greater than changes induced by selenate.
Experiment 2 used 2 µg Se/g diet as selenite and DMH as
the carcinogen. Reddy et al. (1996)
studied selenite
inhibition of azoxymethane, a DMH metabolite, and found a rather modest
decrease in ACF in rats with a much greater intake of Se. Rats fed 4.1
µg/g had a mean of 70 ACF/colon, compared with 117 in rats
fed 0.1 µg/g Se. Consequently, it is possible that Se as
selenite fed at concentrations of 1–2 µg/g has relatively
little effect on ACF formation in rats with carcinogenesis induced by
DMH and its metabolites.
Selenium "bioavailability" has been assessed traditionally by the
ability to replete tissue Se stores and GSH-Px activities. We
reported previously that Se from high Se broccoli was less effective in
restoring GSH-Px activity and Se concentrations in most organs and
tissues of Se-depleted rats (Finley 1998
). By such a
criterion, Se from high Se broccoli should be less "bioavailable"
than selenate or selenite. Although bioavailablity may confer a
specific connotation to many, to others it is used synonymously with
"biological usefulness." This study, as well as the studies of
mammary cancer and high Se garlic (Ip and Lisk 1994a
, 1994b
and 1995
), demonstrates that the least bioavailable Se compounds
may have some of the most potent biological activities. Nutritionists
should keep this in mind when dispensing advice on the optimal forms of
dietary Se.
In summary, we have demonstrated the Se from high Se broccoli is more effective than selenate or selenite for the prevention of precancerous lesions in the colon of rats. The anticarcinogenic activity of Se in broccoli is caused by the unique chemical form of Se in broccoli. A lesser amount of the Se in broccoli may be used to form selenoproteins, thus allowing more to enter a pool that is protective against colon carcinogenesis.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal
opportunity/affirmative action employer and all agency services are available without discrimination.
4 Abbreviations used: AC, aberrant crypts; ACF, aberrant crypt foci; DMABP, 3,2'-dimethyl-4-aminobiphenyl; DMH, dimethyl hydrazine; GSH-Px, glutathione peroxidase; GST, glutathione-S-transferase; RDA, recommended dietary allowance; SeMet, selenomethionine; SeMSC, Se-methyl selenocysteine.
Manuscript received February 9, 2000. Initial review completed March 2, 2000. Revision accepted May 4, 2000.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSExperiment 1Experiment 2DISCUSSIONREFERENCES |
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