Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of auraptene

The modifying effects of auraptene on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all animals, except those with the test chemical alone and control rats, received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the end of the study (20 weeks), 75% of the rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups who received a dose of 500 ppm auraptene during the initiation phase developed significantly reduced incidence of tumors (39%; P<0.05). Exposure to auraptene (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (29%; P<0.01). The reduction of the incidence of severe dysplasia was obtained when auraptene was administered in the post-initiation phase (P<0.05). Cell proliferation in the esophageal epithelium determined by proliferating cell nuclear antigen (PCNA) was lowered by auraptene (P<0.01). Blood polyamine contents in rats who received NMBA and the test compound were also smaller than those of rats that received the carcinogen (P<0.05). These findings suggest that dietary auraptene is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation as well as post-initiation phases, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.     

Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis: down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun

Our laboratory has used a rodent model of human esophageal squamous cell carcinoma to identify putative chemopreventive agents for this disease and to determine their mechanisms of action. In the present study, we treated F344 rats with the esophageal carcinogen, N-nitrosomethylbenzylamine (NMBA), thrice per week for 5 weeks. Beginning 1 week later, they were fed a synthetic diet containing 5% black raspberries (BRB) for the duration of the bioassay (25 weeks). Rats were sacrificed at weeks 9, 15, and 25. Esophageal tissues were collected, and tumor data were recorded. The expression and enzymatic activities of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of c-Jun in the esophagi, were evaluated to investigate the mechanism(s) by which black raspberries modulate tumorigenesis. At week 25, BRB inhibited tumor multiplicity, the standard end point in this tumor model, from 3.78 +/- 0.41 tumors per rat in NMBA-treated animals to 2.23 +/- 0.21 tumors per rat in animals treated with NMBA plus BRB (P < 0.005). BRB reduced mRNA and protein expression levels of COX-2, iNOS, and c-Jun as well as the level of prostaglandin E(2) in preneoplastic lesions of the esophagus at week 25. The berries inhibited mRNA expression of iNOS and c-Jun, but not COX-2, in papillomatous lesions of the esophagus. Prostaglandin E(2) and total nitrite levels were also decreased by BRB in papillomas. These results suggest a novel tumor suppressive role of BRB through inhibition of COX-2, iNOS, and c-Jun.     

Inhibition of N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in rats by green and black tea

In this study, we investigated the effects of green tea andblack tea, when given either during or after carcinogen treatment,on esophageal tumorigenesis in male Sprague—Dawley rats.Rats were treated with N-nitrosomethylbenzylamine (NMBzA) (2.5mg/kg, s.c., twice weekly) for 5 weeks; 39 weeks after the initialdose of NMBzA, 65% of the rats had esophageal tumors with anaverage of 1.4 0.3 tumors per rat. In the groups of rats receiving0.6% of decaffeinated green tea (DGT) or decaffeinated blacktea (DBT) (6 mg tea solids/ml) as the sole source of drinkingfluid during the NMBzA-treatment period, esophageal tumor incidenceand multiplicity were reduced by     

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.     

Chemoprevention of colon cancer by dietary fatty acids

During the last two decades, substantial progress has been made in the understanding of the relationship between the dietary constituents and development of colon cancer in man. Unlike studies of cancer among smokers and nonsmokers, nutritional epidemiologic studies are confronted with the inherent difficulty of assessing reasonably precise exposures. The lack of consistency between international correlation studies and case-control studies does not necessarily negate a dietary etiology of colon cancer because these inconsistencies may have arisen, at least in part, from methodological limitations. Some of these deficiencies in epidemiological studies of diet and cancer have been corrected; recent case-control studies demonstrated that high dietary fat is a risk factor for colon cancer development and that an overall increase in intake of foods high in fiber might decrease the risk for colon cancer. The results of epidemiologic studies may be assumed to present conservative estimates of the true risk for cancer associated with diet. The populations with high incidence of colon cancer are characterized by high consumption of dietary fat, which may be a risk factor in the absence of factors that are protective, such as whole-grain cereals and of other high-fiber. Laboratory animal model studies have shown that certain dietary lipids and fibers influence tumorigenesis in the colon. The data of metabolic epidemiological and laboratory animal model studies are sufficiently convincing with recpect to enhancement of colon cancer by type of fat and protection by certain dietary fibers.     

Mechanistic basis for the chemopreventive effects of black raspberries at a late stage of rat esophageal carcinogenesis

The present study used a postinitiation protocol to investigate molecular mechanisms by which black raspberries (BRBs) influence the late stages of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats. F344 rats were injected with NMBA and then fed either control diet or a diet containing 5% BRB powder. Control rats were injected with DMSO/water (20:80), the vehicle for NMBA. Esophagi from control, NMBA- and NMBA?+?BRB-treated rats were collected at 35 wk for histopathological, molecular, and immunohistochemical analyses. Treatment with 5% BRBs reduced the number of dysplastic lesions and the number and size of esophageal papillomas in NMBA-treated rats. When compared to esophagi from control rats, NMBA treatment led to the differential expression of 4807 genes in preneoplastic esophagus (PE) and 17?846 genes in esophageal papillomas. Dietary BRBs modulated 626 of the 4807 differentially expressed genes in PE and 625 of the 17?846 differentially expressed genes in esophageal papillomas towards normal levels of expression. In both PE and in papillomas, BRBs modulated the mRNA expression of genes associated with carbohydrate and lipid metabolism, cell proliferation and death, and inflammation. In these same tissues, BRBs modulated the expression of proteins associated with proliferation, apoptosis, inflammation, angiogenesis, and both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Interestingly, matrix metalloproteinases involved in tissue invasion and metastasis, and proteins associated with cell-cell adhesion, were also modulated by BRBs. This is the first report of the effects of berries on the expression of genes associated with the late stages of rat esophageal carcinogenesis.     

Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy

This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods.     

Chemoprevention of mammary tumorigenesis by a combined regimen of selenium and vitamin A

Mammary tumorigenesis induced in rats by 7,12-dimethylbenz[a]anthracenewas markedly suppressed by combined dietary supplementationwith sodium selenite and retinyl acetate; final tumor yieldwas reduced to 8% of control as compared with 51% and 36%, respectively,for selenium and retinyl acetate alone. A continuous intakeof both agents was necessary to sustain the chemopreventiveeffect.     

Weak enhancing effects of simultaneous ethanol administration on chemically induced rat esophageal tumorigenesis

Excessive alcohol consumption is associated epidemiologically with an elevated risk of esophageal cancer. In this study, we examined the effects of simultaneous administration of ethanol on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Groups 1-3 were treated with NMBA at a dose of 0.5 mg/kg body weight (high dose), and groups 4-6 received a dose of 0.1 mg/kg body weight (low dose), by s.c.-injection, 3 times per week for the first 5 weeks. Groups 1 and 4 were given ethanol free water as controls. Groups 2 and 5 were treated with 10% ethanol in their drinking water only at the time of NMBA treatment, while groups 3 and 6 were administrated the supplement continuously up to the end of the experiment. Macroscopically, with high dose NMBA-initiation, simultaneous 5-week and continuous 24-week ethanol administration demonstrated a tendency to increase the incidence and multiplicity of tumors, and also microscopically the multiplicity of papillary hyperplasias. In low dose groups, the incidence of esophageal papillary hyperplasias was significantly increased by continuous 24-week ethanol administration. Immunohistochemistry, proliferating cell nuclear antigen (PCNA) positive indices tended to be increased in tumors by simultaneous 5-week and continuous 24-week ethanol administration, but cyclin D1 expression was not affected. These data suggest that simultaneous ethanol administration have weak enhancing effects, and also promoting effects in post-initiation phase is present on NMBA-induced rat tumorigenesis.     

Inhibition of NMU-induced mammary tumorigenesis by dietary soy

We previously demonstrated that female Sprague-Dawley rats fed AIN-93G diets containing soy protein isolate (SPI+) had lower DMBA-induced mammary tumor incidence than those fed diets containing casein (CAS), due partly to altered Phase I metabolism with soy. Here, we evaluated the tumor protective effects of these same diets to the direct-acting carcinogen N-methyl-nitrosourea (NMU). Tumor incidence was reduced and tumor latency was enhanced, in NMU-administered female rats lifetime exposed to SPI+, relative to the CAS group. Tumor multiplicity did not differ with diet, while tumor grade tended to be more advanced with SPI+. Normal mammary glands of CAS and SPI+ tumor-bearing rats had comparable proliferative and apoptotic status. However, mammary expression of HER-2/neu and progesterone receptor (PR) genes was higher for SPI+ rats. Moreover, tumored SPI+ rats had lower serum progesterone levels than those fed CAS, while serum estrogen did not differ. Serum from tumored SPI+ rats had higher apoptotic activity towards mammary epithelial MCF-7 cells, than CAS serum. Thus, dietary soy protects against mammary tumorigenesis induced by a direct-acting carcinogen and alters signaling pathways involving PR and HER-2/neu.     

Chemoprevention of intestinal tumorigenesis by nabumetone: induction of apoptosis and Bcl-2 downregulation

Treatment of MIN mice with the nonsteroidal anti-inflammatory drug, nabumetone, resulted in a dose-dependent suppression of intestinal tumorigenesis. In both the uninvolved MIN mouse colonic epithelium and HT-29 colon cancer cells, nabumetone downregulated the anti-apoptotic protein, Bcl-2, with concomitant induction of apoptosis, suggesting a potential mechanism for colon cancer chemoprevention.     

Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor

The epidermal growth factor receptor (EGFR) is activated in skin cells following UV irradiation, the primary cause of nonmelanoma skin cancer. The EGFR inhibitor AG1478 prevented the UV-induced activation of EGFR and of downstream signaling pathways through c-Jun NH2-terminal kinases, extracellular signal-regulated kinases, p38 kinase, and phosphatidylinositol 3-kinase in the skin. The extent to which the UV-induced activation of EGFR influences skin tumorigenesis was determined in genetically initiated v-ras(Ha) transgenic Tg.AC mice, which have enhanced susceptibility to skin carcinogenesis. Topical treatment or i.p. injection of AG1478 before UV exposure blocked the UV-induced activation of EGFR in the skin and decreased skin tumorigenesis in Tg.AC mice. AG1478 treatment before each of several UV exposures decreased the number of papillomas arising and the growth of these tumors by approximately 50% and 80%, respectively. Inhibition of EGFR suppressed proliferation, increased apoptotic cell death, and delayed the onset of epidermal hyperplasia following UV irradiation. Genetic ablation of Egfr similarly delayed epidermal hyperplasia in response to UV exposure. Thus, the UV-induced activation of EGFR promotes skin tumorigenesis by suppressing cell death, augmenting cell proliferation, and accelerating epidermal hyperplasia in response to UV. These results suggest that EGFR may be an appropriate target for the chemoprevention of UV-induced skin cancer.     

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone

The modifying effects of dietary administration of capsaicin, which is the principal pungent capsicum fruit, and rotenone, which is a naturally occurring pesticide derived from Derris and Lonchorcarpus species, on azoxymethane (AOM)-induced colon tumorigenesis were investigated in male F344 rats. Gavage with capsaicin and rotenone significantly elevated phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. In an aberrant crypt foci (ACF) bioassay, feeding of capsaicin and rotenone at a dose of 500 ppm for 4 weeks significantly inhibited ACF formation induced by AOM (20 mg/kg body weight, once a week for 2 weeks). In a subsequent long-term study designed to confirm the protective effects of both compounds on ACF development, one group was treated with AOM alone and four other groups received the carcinogen treatment plus diets containing 500 ppm test compounds for 4 weeks (initiation phase) and for 34 weeks (post-initiation phase). Two groups were treated with capsaicin or rotenone alone (500 ppm in diet) and one group was maintained on the basal diet. At the termination of the study, dietary exposure of capsaicin during the initiation phase was found to significantly reduce the incidence of colonic adenocarcinoma (60% vs. 24%, 60% reduction, P=0.0407). Rotenone feeding during the post-initiation phase also reduced the frequency of colonic adenocarcinoma (60% vs. 19%, 68% reduction, P=0.0226). Our results suggest that two natural compounds, capsaicin and rotenone, might be useful for the prevention of human colon cancers.     

Inhibition of N'-nitrosonornicotine-induced esophageal tumorigenesis by 3-phenylpropyl isothiocyanate

The ability of dietary isothiocyanates to inhibit the esophageal metabolism of N'-nitrosonornicotine (NNN) was examined in F344 rats. Following feeding of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 3-phenylpropyl isothiocyanate (PPITC), 4- phenylbutyl isothiocyanate (PBITC) or 6-phenylhexyl isothiocyanate for 2 weeks, rats were killed and the esophagi were incubated in vitro with [5-3H]NNN. While dietary BITC, PEITC and PBITC all decreased NNN metabolism, dietary PPITC had the greatest effect, yielding inhibition ranging from 55 to 91% of the control production of various NNN metabolites. To determine the chemopreventive efficacy of PPITC on NNN- induced esophageal tumorigenesis, rats were fed AIN-76A diets containing 0, 1.0 or 2.5 micromol/g PPITC and were given untreated drinking water or drinking water containing 5 p.p.m. NNN. After 87 weeks, the experiment was terminated and the esophageal tumors were counted. Rats that were given untreated drinking water developed no tumors. Rats that were given 5 p.p.m. NNN and unadulterated AIN-76A diet had an esophageal tumor incidence of 71% and a multiplicity of 1.57 tumors/animal. The two dietary concentrations of PPITC reduced the incidence and multiplicity of NNN-induced esophageal tumors by >95%. These results demonstrate the remarkable chemopreventive efficacy of PPITC in the NNN-induced esophageal tumor model.      

Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid

In this report, we describe the ability of ellagic acid (EA), a phenolic compound present in a number of fruits and nuts, to inhibit N-nitrosobenzylmethylamine (NBMA) tumorigenesis in the rat esophagus. When administered in a semi-purified diet at concentrations of 0.4 and 4 g/kg, EA produced a significant (21-55%) decrease in the average number of NBMA-induced esophageal tumors after 20 and 27 weeks of the bioassay. EA exhibited inhibitory effects toward preneoplastic lesions as well as neoplastic lesions. Tumors were not observed in vehicle-control rats or in rats that received EA alone.     

Enhancement of estrogen-induced renal tumorigenesis in hamsters by dietary iron

Iron participates in the generation of hydroxyl radicals by the iron- catalyzed Fenton reaction. Its role in estrogen-induced carcinogenesis has been examined in this study by investigating the effects of iron content of hamster diets on tumor induction by estradiol. The renal tumor incidence and number of tumor nodules in hamsters treated with estradiol plus a diet enriched with iron (384 p.p.m. Fe as ferric citrate) for 5 months were 2- and 4-fold higher, respectively, than those observed in animals on an iron-poor diet plus estradiol (3.9 p.p.m. Fe, as ferric citrate). Tumor incidence and number of tumor nodules in estradiol-treated hamsters on the iron-deficient diet were not different from those of animals on a normal rodent chow. No tumors were detected in hamsters treated only with the low or high iron diets. Total serum iron was significantly increased in animals treated with the high iron diet plus estradiol compared with the low iron diet plus estradiol group and the high and low iron controls. Estrogen treatment increased non-heme iron in liver of both high and low iron treatment groups and in kidney of the hamsters on the low iron diet. It is concluded that dietary iron enrichment enhances the incidence and severity of estrogen-induced tumor induction.      

Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion

Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N-methylurea (2x50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1% pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or 100 days (promotion) after carcinogen injection. The onion diet given during initiation reduced the number of AOM-induced ACF (60 versus 86, p=0.03), and the size of IQ-induced ACF (1.33 versus 1.97, p=0.02). Given post-initiation, the onion diet reduced the number of ACF (34 versus 59, p=0.008) and of large ACF (6 versus 15, p=0.02). Phytochemicals diet and pluronic diet reduced ACF growth similarly. Data show that a 5% onion diet reduced carcinogenesis during initiation and promotion stages, and suggest this chemoprevention is due to known phytochemicals.     

Interaction of dietary fat and route of carcinogen administration on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats

Since the results of an earlier study indicating no effect ofdietary fat on dimethylhydrazine (DMH)-induced colon cancerin rats differed from those of other investigators, the presentstudy was initiated to determine if the modulating effect offat intake on colon tumorigenesis was dependent on the routeof DMH administration. Male weanling Sprague-Dawley rats (160)were fed one of two nutritionally balanced diets containing5% or 24% corn oil (CO). Following 3 weeks adaptation to theirrespective diets, 40 rats from each diet group were treatedwith five doses of DMH (30 mg/kg) by intragastric i.g.) gavageor subcutaneous (s.c.) injection, over a 3 week period. Ratswere sacrificed when they showed clinical signs of colon tumorand surviving animals were killed 51 weeks after the initialDMH treatment. The cumulative probability of death with coloncarcinoma did not differ between the dietary or treatment groups.There was no effect of route of administration or dietary faton total intestinal tumor incidence. The number of rats withcolon carcinoma was: 5%CO.IG=25; 24%CO.IG=27; 5%CO.SC=23; 24%CO.SC=19.Polypoid tumor incidence was significantly higher in the 24%CO.SCgroup (12/40) compared to the 5%CO.SC group (3/40) (Chi-squared= 5.25; p <0.03) while sessile tumor incidence was the inverse.Marginally significant differences in tumor morphology werenoted between the IG groups.     

Chemoprevention of colorectal cancer: dietary and pharmacologic approaches

Colorectal cancer is a major cause of death in the United States, where it accounts for approximately 57,000 deaths per year. Thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as the use of natural or pharmacologic agents to disrupt the process of carcinogenesis. Substances explored as chemopreventive agents in colorectal cancer include: (1) the nonsteroidal anti-inflammatory drugs (NSAIDS), which may inhibit the evolution and formation of adenomas by their inhibition of cyclooxygenase and decrease of prostaglandin synthesis; (2) antioxidants, such as vitamin E or C, which may modulate carcinogenic substances; and (3) folate and calcium, which may interfere with tumor cell growth and replication. Dietary intervention can be accomplished by decreasing fat intake and increasing fiber consumption, both of which have been linked to a lower incidence of colon cancer in multiple epidemiologic studies. This field is continuing to evolve. Hopefully, ongoing research efforts will offer a better understanding of the role of these and other substances in chemoprevention. This article summarizes the available data regarding dietary and pharmacologic approaches to colorectal cancer chemoprevention.     

SHORT COMMUNICATION: Inhibition of rat mammary tumorigenesis by dietary cholesterol

The effects of dietary cholesterol and oxidized cholesterolon mammary tumor development were examined in female Sprague-Dawleyrats exposed to the carcinogen N-methyl-N-nitrosourea (MNU).Animals were administered 50 mg/kg MNU at 50 days of age andfed either a control (AIN-76) diet or the control diet supplementedwith 0.3% cholesterol or 0.3% oxidized cholesterol for up to26 weeks. The oxidized cholesterol was prepared by heating cholesterolat 110°C for 48 h. Gas chromatographic analysis of the oxidizedcholesterol revealed a 2% yield of oxidation products in additionto a large amount of unchanged cholesterol (>96%). Tumorincidence in the cholesterol group (67%) was significantly lowerthan in the control group (96%, P <0.05), but the oxidizedcholesterol group (79%) was not significantly different fromthe control or cholesterol groups. Average number of tumorsper animal was lower in the cholesterol group (1.5) than inthe control (2.8) or oxidized cholesterol groups (2.3, P <0.005).Serum low density lipoprotein (LDL) cholesterol was greaterin the cholesterol (185± 38 mg/dl) and the oxidized cholesterolgroups (160± 34 mg/dl) than in the control (55±4 mg/ dl, P <0.05), although there was no difference betweenthe cholesterol and the oxidized cholesterol groups. These resultsshow that dietary cholesterol inhibits mammary tumor developmentin this model. Elevated serum LDL cholesterol may inhibit denovo cholesterol synthesis in preneoplastic and/or tumor cells,thereby inhibiting their proliferation.