Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction.

The effect of green tea polyphenol fraction (GTP) on azoxymethane(AOM)-induced colon carcinogenesis was investigated in male Fischer rats. The rats were given AOM (7.4 mg/kg body weight) s.c. once a week for 10 weeks. A week after the treatment, they were divided into three groups: AOM-control (26 rats), AOM-GTP1 (26 rats) and AOM-GTP2 (25 rats). AOM-GTP1 and AOM-GTP2 groups respectively received 0.01 and 0.1% GTP in drinking water from week 11 to 26. AOM-control group received tap water throughout this experiment. Autopsy on week 26 showed that tumor incidence and average numbers of tumors per rat in the AOM-GTP1 and AOM-GTP2 groups were significantly lower than those of the AOM-control group: 38.1% and 47.6% versus 77.3%; 0.6 and 0.7 versus 1.5. Thus, it was concluded that GTP inhibited the development of AOM-induced colon carcinogenesis. The inhibition by GTP did not show significant dose dependence.     

Triamterene Suppresses Bombesin-enhanced Peritoneal Metastasis of Intestinal Adenocarcinomas Induced by Azoxymethane

The effects of combined administration of bombesin and the diuretic triamterene on the incidence of peritoneal metastasis of intestinal cancers induced by azoxymethane (AOM) and the labeling index of intestinal cancers were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of AOM (7.4 mg/kg body weight) for 10 weeks and s.c. injections of bombesin (40 μg/kg body weight) every other day, and from week 16, s.c. injections of triamterene (10 and 20 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of both doses of triamterene with bombesin had little or no influence on the enhancement of intestinal carcinogenesis by bombesin, or the location, histologic type, depth of invasion, or labeling index of intestinal cancers, it significantly reduced the incidence of cancer metastasis. These findings indicate that triamterene suppresses cancer metastasis through a mechanism that does not affect the proliferation of intestinal cancers.     

Inhibition of Azoxymethane-induced Colon Carcinogenesis in Rat by Green Tea Polyphenol Fraction

The effect of green tea polyphenol fraction (GTP) on azoxymethane(AOM)-induced colon carcino-genesis was investigated in male Fischer rate. The rats were given AOM (7.4 mg/kg body weight) s.c. once a week for 10 weeks. A week after the treatment, they were divided into three groups: AOM-control (26 rats), AOM-GTP1 (26 rats) and AOM-GTP2 (25 rats). AOM-GTPl and AOM-GTP2 groups respectively received 0.01 and 0.1% GTP in drinking water from week 11 to 26. AOM-control group received tap water throughout this experiment. Autopsy on week 26 showed that tumor incidence and average numbers of tumors per rat in the AOM-GTPl and AOM-GTP2 groups were significantly lower than those of the AOM-control group: 38.1% and 47.6% versus 77.3%; 0.6 and 0.7 versus 1.5. Thus, it was concluded that GTP inhibited the development of AOM-indnced colon carcinogenesis. The inhibition by GTP did not show significant dose dependence.     

Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced intestinal carcinogenesis in F344 rats

Butyrate exerts anti-tumour effects in vitro, but not consistently in vivo. We previously demonstrated that the administration of slow-release gastro-resistant pellets of sodium butyrate increases apoptosis in the colon mucosa of rats, an effect which may protect against carcinogenesis. Therefore, we studied whether the administration of butyrate pellets could protect rats against experimental colon carcinogenesis. Four to 5 week old male F344 rats were fed a high-fat (HF) diet (230 g/kg corn oil w/w) and treated s.c. with two injections (one week apart) of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight or saline. Rats were then divided into two groups: one group received sodium butyrate pellets mixed into the diet (1.5% w/w) for 33 weeks (150 mg butyrate/day) and the second group received the high-fat diet with no butyrate. Administration of sodium butyrate pellets in the diet did not significantly affect colon carcinogenesis: the number of intestinal tumours/rat was 1.6 +/- 0.2 in controls and 2.1 +/- 0.2 in butyrate-fed rats (means +/- SE; P = 0.22, by ANOVA), while the incidence of intestinal tumours was 79 (23/29) and 90% (27/30) in controls and in butyrate-fed rats, respectively (P = 0.29 by Fisher's exact test). The level of apoptosis in the tumours was not affected by butyrate, nor was the expression of p21(CIP), a cell cycle-related protein. In conclusion, the current study indicates that butyrate does not protect against AOM-induced colon carcinogenesis in rats.     

Inhibition by dietary benzylselenocyanate of hepatocarcinogenesis induced by azoxymethane in Fischer 344 rats

The effect of dietary benzylselenocyanate (BSC), a novel organoselenium compound and its sulfur analog, benzylthiocyanate (BTC), on hepatocarcinogenesis induced by azoxymethane (AOM) was investigated in male F344 rats. Eighty-one weanling rats were divided into 3 groups and were raised on a semipurified diet (control diet). Starting from 5 weeks of age, groups of animals consuming the control diet were fed one of the experimental diets containing 25 ppm BSC or BTC. An additional group was continued on the control diet. At 7 weeks of age, animals were given weekly sc injections of AOM (15 mg/kg body weight once weekly for 2 weeks). One week after the second AOM injection, those groups receiving BSC and BTC diets were transferred to the control diet and continued on this diet until termination of the experiment at 34 weeks after the last AOM injection. For quantitative analysis of enzyme-altered liver cell foci, glutathione S-transferase placental form was stained by an immunohistochemical technique. The results indicate that the incidence and the density of the enzyme-altered foci were significantly lower in AOM-treated rats fed the diet containing 25 ppm BSC (foci incidence 56%, foci density 2.43/cm2) than in AOM-treated animals fed the control diet (foci incidence 92%, foci density 4.79/cm2). The incidence of small altered foci was significantly inhibited in rats fed the BTC diet (35%) as compared to those fed the control diet (68%), but the degree of inhibition was more pronounced in animals fed the BSC diet than in those fed the BTC diet.     

Suppression of azoxymethane-induced rat colon carcinoma development by a fish oil component, docosahexaenoic acid (DHA)

The effects of intragastric gavage administration of docosahexaenoic acid (DNA) , a major component of fish oil, on azoxymethane (AOM)- induced colon carcinogenesis in rats was investigated. Male F344 rats were treated with 15 mg/kg body wt of AOM once a week, for two weeks. The animals were given either 1 ml of DHA or water intragastrically 5 times a week, starting the day before the first carcinogen treatment. The numbers of AOM-induced aberrant crypt foci in the rats given DHA were 76% and 62% of the control values, at 4 and 12 weeks, respectively. After 36 weeks of DHA treatment, colon tumors were counted and examined histologically. The blood plasma levels of prostaglandin E2 (PGE2) and polyunsaturated fatty acids were also quantified. The incidences of colon cancer did not differ, being 96% and 92% in the AOM and AOM+DHA groups, respectively. Colon cancer multiplicity was, however, significantly decreased by the DHA treatment; 3.65 +/- 2.18 in the AOM group and 2.41 +/- 1.58 in the AOM+DHA group (P <0.01). Notably, the numbers of moderately differentiated adenocarcinomas in the middle and distal colon in the DHA-treated group were lower than in the AOM group. The levels of PGE2 and arachidonic acid in the blood plasma of DHA-treated rats were also significantly lower than in the AOM group. These results suggest that DHA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting the arachidonic cascade.      

Pomegranate (Punica granatum) Peel Extract Efficacy as a Dietary Antioxidant against Azoxymethane-Induced Colon Cancer in Rat

Functional foods include antioxidant nutrients which may protect against many human chronic diseasesby combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigatethe protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumorsin rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly dividedinto 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM orinjected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM andPPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After thelast AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At theend of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examinedmicroscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemicalmeasurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci inthe PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked theAOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissuehomogenates. The results suggest that PPE can partially inhibit the development of colonic premalignantlesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improvingthe redox status of colonic cells.     

A rapid dual organ rat carcinogenesis bioassay for evaluating the chemoprevention of breast and colon cancer

In this study we evaluated the effect of dietary administration of a high fat, low fiber diet (HRD) with or without 2% phytic acid (PA) on the development of mammary cancer and/or colon cancer in rats exposed to methylnitrosourea (MNU), azoxymethane (AOM) or MNU + AOM. The rats were fed a HRD alone or a HRD + 2% PA. At the end of week 2, the rats were given either a s.c. injection of MNU (50 mg/kg body wt) or one of normal saline (vehicle). At the end of weeks 3 and 4, the rats were given either a s.c. injection of AOM (15 mg/kg body wt per week) or one of normal saline (vehicle). Nine weeks after the injection of MNU or saline, 10 rats from each group were sacrificed and the mammary tumor incidence and the number of colonic aberrant crypt foci (ACF) were compared between different groups. The administration of different diets was continued for an additional 21 weeks and the mammary tumor and colon tumor incidence between different groups were compared. Results showed that rats injected with MNU alone did not develop ACF or colon tumors while those injected with AOM alone did not develop mammary tumors. Linear regression analysis of the number of ACF at 11 weeks versus colonic tumor incidence at 32 weeks, and the linear regression analysis of mammary tumor incidence at 11 weeks versus mammary tumor incidence at 32 weeks, both showed good linear correlation. These results demonstrate the potential value of the short term dual organ carcinogenesis bioassay for screening chemopreventive agents for their relative ability to inhibit the development of mammary cancer and/or colon cancer while on high risk diet.     

Inhibition by Dietary Benzylselenocyanate of Hepatocarcinogenesis Induced by Azoxymethane in Fischer 344 Rats1

The effect of dietary benzylselenocyanate (BSC), a novel organoselenium compound and its sulfur analog, benzylthiocyanate (BTC), on hepatocarcinogenesis induced by azoxymethane (AOM) was investigated in male F344 rats. Eighty-one weanling rats were divided into 3 groups and were raised on a semipurificd diet (control diet). Starting from 5 weeks of age, groups of animals consuming the control diet were fed one of the experimental diets containing 25 ppm BSC or BTC. An additional group was continued on the control diet. At 7 weeks of age, animals were given weekly sc injections of AOM (15 mg/kg body weight once weekly for 2 weeks). One week after the second AOM injection, those groups receiving BSC and BTC diets were transferred to the control diet and continued on this diet until termination of the experiment at 34 weeks after the last AOM injection. For quantitative analysis of enzyme-altered liver cell foci, glutathione S-transferase placental form was stained by an immunohistochemical technique. The results indicate that the incidence and the density of the enzyme-altered foci were significantly lower in AOM-treated rats fed the diet containing 25 ppm BSC (foci incidence 56%, foci density 2.43/cm²) than in AOM-treated animals fed the control diet (foci incidence 92%, foci density 4.79/cm²). The incidence of small altered foci was significantly inhibited in rats fed the BTC diet (35%) as compared to those fed the control diet (68%), but the degree of inhibition was more pronounced in animals fed the BSC diet than in those fed the BTC diet.     

Effect of restricted caloric intake on azoxymethane-induced colon tumor incidence in male F344 rats

The effect of 30% caloric restriction on azoxymethane (AOM)-induced colon carcinogenesis was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt, once weekly for 2 weeks). Four days after the second AOM injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received same amounts of fiber, vitamins, and minerals. Thirty-two weeks after AOM injections, all animals were necropsied. The animals in the calorie-restricted group developed significantly fewer colon tumors and had a lower colon tumor incidence than did the rats in the ad libitum group. The size of colon tumors was also reduced in the calorie-restricted group.     

Enhancement by vasoactive intestinal peptide of experimental carcinogenesis induced by azoxymethane in rat colon

The effects of vasoactive intestinal peptide (VIP) on the incidence and histology of colonic tumors induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 20 micrograms/kg body weight of VIP every other day for 12 weeks and from experimental week 3, were given 10 weekly injections of 7.4 mg/kg body weight of AOM. The administration of VIP before and during AOM treatment resulted in a significant increase in the incidence of colonic tumors in week 40. Furthermore, it caused a significant increase in the labeling index of the colonic mucosa during AOM treatment. These findings indicate that VIP enhanced the development of colonic tumors. This effect may have been related to its effect in increasing proliferation of cells in the colonic mucosa during administration of the carcinogen.     

Chemopreventive effect of 2-(allylthio)pyrazine (2-AP) on rat colon carcinogenesis induced by azoxymethane (AOM)

An investigation was conducted to assess the chemopreventive effects of 2-(allylthio)pyrazine (2-AP), synthesized for potential use as a chemopreventive agent, after administration during the pre-initiation and post-initiation stages in a rat colon carcinogenesis model with azoxymethane (AOM). One hundred, 5-week-old, male F344 rats were randomly divided into two experiments (n = 50 each). Experiment 1 rats were randomly divided into three groups: Group 1 rats were pre-treated with 2-AP (25 or 50 mg/kg body weight, 3 consecutive days through the route of intragastric intubations) before AOM (20 mg/kg body weight, single subcutaneous (s.c.) injection) initiation. Group 2 rats were treated with AOM alone. Group 3 rats were given 2-AP alone without AOM initiation. The animals were killed at the end of each experiment (week 5) and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Experiment 2 rats were randomly divided into three groups: Group 1 rats were given 2-AP (10, 25 or 50 mg/kg body weight, five-times intragastric intubations per week for 5 weeks from week 3) after AOM (15 mg/kg body weight, three s.c. injections) initiation for 2 weeks. Group 2 rats were treated with AOM alone. Group 3 rats were given 2-AP alone without AOM initiation. The animals were killed at the end of the experiment (week 8) and the ACF of the colonic mucosa were quantified. Total numbers of ACF/colon in Group 1 rats (pre-treated with 2-AP) tended to decrease (2-AP, 50 mg/kg body weight) or increase (2-AP, 100 mg/kg body weight) depending on the dose level. Total numbers of ACF/colon in Group 1 rats (treated with AOM followed by 2-AP, all subgroups; 160.8 +/- 38.0; 161.8 +/- 38.1; 137.1 +/- 48.4) were decreased significantly compared with the values in Group 2 rats (AOM alone; 214.8 +/- 48.1) (P < 0.05 or 0.01). The highest dose group (2-AP, 50 mg/kg body weight) had the lowest levels of total numbers of ACF/colon among the three subgroups. Total numbers of aberrant crypts (AC)/colon of the highest dose group (340.1+/- 117.9) decreased significantly compared with the value for Group 2 rats (AOM alone; 545.1 +/- 38.3). These results thus suggest that 2-AP may have potential as a chemopreventive agent against rat colon carcinogenesis after administration of AOM during the post-initiation stage.     

Inhibition of O(6)-methylguanine-DNA methyltransferase increases azoxymethane-induced colonic tumors in rats

Azoxymethane (AOM) causes O(6)-methylguanine adduct formation which leads to G-->A transitions. Their repair is carried out by O(6)-methylguanine-DNA methyltransferase (MGMT). To evaluate the importance of this repair event in AOM-induced carcinogenesis, we examined the effect of O(6)-benzylguanine (BG), a potent inhibitor of MGMT, on colonic tumor development. Rats were treated weekly for 2 weeks at 0 and 24 h with BG (60 mg/kg body wt i.p.) or vehicle (40% polyethylene glycol, PEG-400), followed 2 h after the first dose of BG with AOM (15 mg/kg body wt) or vehicle (saline) i.p. Rats were killed 35 weeks later and tumors harvested and DNA extracted. In the AOM-treated groups, BG caused a significant increase in tumor incidence with tumors in 65.9%, versus 30.8% in the AOM/PEG-treated group (P < 0.05). In the BG/AOM group there was also a significant increase in tumor multiplicity, with 2.3 tumors/tumor-bearing rat, versus 1.6 tumors/tumor- bearing rat in the AOM/PEG group (P < 0.05). Since O(6)-methylguanine adducts can cause activating mutations in the K-ras and beta-catenin genes, we examined the effects of BG on these mutations. In the BG group there were seven mutations in codon 12 or 13 of exon 1 of the K-ras gene in 51 tumors examined, compared with no K-ras mutations in 17 tumors analyzed in the AOM/PEG group (P = 0.12). In the BG/AOM group there were 10 mutations in exon 3 of the beta-catenin gene among 48 tumors evaluated, compared with six mutations in 16 tumors analyzed in the PEG/AOM group (P = 0.16). In summary, MGMT inhibition increases AOM-induced colonic tumor incidence and multiplicity in rats.     

Inhibition by dietary organoselenium, p-methoxybenzene-selenol, of hepatocarcinogenesis induced by azoxymethane in rats

The effect of dietary p-methoxybenzeneselenol, a new organoselenium compound, on azoxymethane (AOM)-induced hepatocarcinogenesis was examined in female F344 rats. Semipurified diets containing 0 and 5 ppm p-methoxybenzeneselenol were fed to the rats, starting at 5 weeks of age until one week after the carcinogen treatment. At 7 weeks of age, all animals except the vehicle-treated controls were given weekly sc injections of AOM (15 mg/kg body weight, 3 times). At 34 weeks after the last AOM treatment, the liver neoplasm incidence and liver tumor multiplicity as well as the incidence of altered liver cell foci were significantly lower in AOM-treated rats fed the diet containing 50 ppm p-methoxybenzeneselenol (tumor incidence 19%, tumor multiplicity 0.45/rat, foci incidence 3.47/cm2) than in AOM-treated animals fed the diet without p-methoxybenzeneselenol (tumor incidence 66%, tumor multiplicity 2.24/rat, foci incidence 12.08/cm2). These results indicate that dietary p-methoxybenzeneselenol at a dose of 50 ppm inhibits AOM-induced hepatic tumorigenesis.     

Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).     

A water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia suppresses azoxymethane-induction of colon cancers in male F344 rats

The present study was designed to investigate the protective effect of a dietary water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi or Mannentake) mycelia (designated as MAK) on the induction and development of azoxymethane (AOM)-induced colon tumors in male F344/Du Crj rats. A total of 80 animals were divided into five groups at six weeks of age, groups 2, 3 and 4 being given weekly subcutaneous injections of AOM (15 mg/kg body weight) for the initial 3 weeks to induce colon tumors. Rats in group 1 and 5 were injected with the vehicle, 0.9% (w/v) saline, following the same schedule. Rats in groups 1, 2, 3, 4 and 5 were fed MF, MF, 1.25% MAK, 2.5% MAK and 2.5% MAK diets, respectively, starting 1 week before AOM treatment and throughout the six-month experimental period. There were no significant differences in number of ACF, total AC and AC per site among groups 2 to 4, but the tumor incidence was significantly lower, and tumor size was smaller in group 4 (AOM + 2.5% MAK) than in group 2 (AOM + MF). Additionally, beta-catenin positive tumor cell nuclei were significantly decreased in the MAK-fed rats (groups 3 and 4), which also demonstrated lowering of the PCNA labeling index and a shortened germinal region in the colon. The present results thus indicate that dietary MAK could act as a potent chemopreventive agent for colon carcinogenesis.     

Promotion of intestinal carcinogenesis by dietary methionine

The metabolism of the polyamines spermidine and spermine is known to be enhanced in rapidly proliferating cells. Methionine is a precursor of the aminopropyl moieties of these amines. Therefore, it was of interest to study the effects of a methionine supplemented diet on polyamine metabolism and preneoplastic changes occurring in the intestinal tract of rats treated with the chemical carcinogen azoxymethane (AOM). Adult Wistar rats received 15 mg AOM/kg body wt (i.p.) once each week for 2 weeks. Thereafter, the rats were randomly divided into two groups and received controlled isoenergetic diets containing the same amount of folate, choline and vitamin B12 during 12 weeks: one group was kept on a standard diet; the other was fed the same diet, except that 1% L-methionine was added at the expense of carbohydrates. After 12 weeks, the administration of the methionine-supplemented diet stimulated the turnover rate of ileal epithelial cells, indicating enhanced crypt cell proliferation. Furthermore, in this group, a 2-fold increase in the number of aberrant hyperproliferative crypts and the appearance of tumors was observed in the colon. These effects were accompanied by the increased formation of spermidine and spermine due to the enhancement of S-adenosylmethionine decarboxylase activity and by the upregulation of Cdx-1, a homeobox gene with oncogenic potentials. The experimental data do not support the view of a chemopreventive effect of dietary methionine supplementation on intestinal carcinogenesis in rats, even at an early phase of preneoplastic development, but rather suggest that methionine promotes intestinal carcinogenesis.     

Preventive Effects of a Flavonoid Myricitrin on the Formation of Azoxymethane-induced Premalignant Lesions in Colons of Rats

The preventive effect of dietary exposure to a flavonoid myricitrin of azoxymethane (AOM)-induced aberrantcrypt foci (ACF) and beta-catenin-accumulated crypts (BCAC) formation was investigated in male F344 rats.Thirty-four rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneousinjections of AOM (15 mg/kg body weight) once a week for 3 weeks. Starting 1 week before the first injection ofAOM, rats in groups 2 and 3 were fed a diet containing 500 or 1000 ppm myricitrin, respectively, for 11 weeks.Rats in group 4 were fed a diet containing 1000 ppm myricitrin. Rats in groups 1 and 5 were given the basal dietalone during the study. The experiment was terminated 11 weeks after the start. The frequency of ACF per colonin group 3 treated with AOM and 1000 ppm myricitrin was significantly lower than that in group 1 treated withAOM alone (p<0.01). Furthermore, dietary myricitrin at both doses (groups 2 and 3) significantly inhibited theformation of BCAC when compared to group 1 (p<0.05). These results indicate that myricitrin had possiblechemopreventive effects in the present short-term colon carcinogenesis bioassays and suggest that longer exposuremay cause suppression of tumor development.     

Effect of different levels of dietary trans fat or corn oil on azoxymethane-induced colon carcinogenesis in F344 rats

The effect of various levels of dietary corn oil or trans fat on azoxymethane (AOM; CAS: 25843-45-2)-induced carcinogenesis was investigated in female F344 rats fed the AIN-76 semipurified diets. Starting at 5 weeks of age, groups of rats were fed the low-fat diet containing 5% corn oil (designated as low-fat control diet). At 7 weeks of age, all animals except the vehicle-treated controls, were given sc injections of AOM (15 mg/kg body wt, once weekly) for 3 weeks. After 1 week, groups of animals were transferred to semipurified diets containing 13.6% corn oil and 23.5% corn oil or high-fat diets containing 5.9% corn oil plus 5.9% trans fat plus 11.8% Oleinate (low trans fat), 5.9% corn oil plus 11.8% trans fat plus 5.9% Oleinate (intermediate trans fat), and 5.9% corn oil plus 17.6% trans fat (high trans fat). Fecal bile acids were measured in vehicle-treated rats. All animals were necropsied 34 weeks after the last AOM injection. The animals fed the 23.5% corn oil diet had a higher incidence of colon tumors than did those in the groups fed the 5 and 13.6% corn oil diets. There was no difference in colon tumor incidence between the 5 and 13.6% corn oil diet groups. The animals fed the high-fat diets containing low trans fat, intermediate trans fat, and high trans fat developed significantly fewer liver and colon tumors and more small intestinal tumors than did the rats fed 23.5% corn oil diet. The excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid was higher in animals fed the 23.5% corn oil diet compared to the excretion in animals fed the other diets.