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PubMed1985

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.

Animals↗
PubMed1986

Effects of dietary saturated and unsaturated fatty acids on fecal bile acids and colon carcinogenesis induced by azoxymethane in rats.

To determine whether the kind of dietary fat affects colon carcinogenesis, male Donryu rats were fed a 5% fat diet containing linoleate, an unsaturated fat, or stearate, a saturated fat, in semipurified fat-free chow. The rats were given azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and killed 15 weeks after the last injection of the carcinogen. The rats on the unsaturated fat diet had a significantly higher incidence of colon tumors. Fatty acid analysis of cholesterol esters in the liver and examination of the amount of fecal bile acids showed that the unsaturated fat diet increased the level of cholesterol linoleate and arachidonate in the liver and also increased the fecal excretion of bile acids, especially that of lithocholic acid. The colon tumors in rats on the unsaturated fat diet, compared with those in rats on the saturated fat diet, contained a higher level of lysophosphatidylcholine. These results suggest that increased fecal excretion of bile acids due to increased polyunsaturated cholesterol esters in the liver stimulates phospholipase A2 activity of colon initiated cells and enhances colon carcinogenesis in rats on the unsaturated fat diet.

Animals↗
PubMed1979

Promotion of azoxymethane-induced intestinal cancer by high-fat diet in rats.

Promotional properties of a high-fat diet in intestinal cancer were studied by feeding a 30% beef fat diet to 8 groups of rats (25 rats/group) for time periods varying from 1 to 21 weeks after 8 weekly s.c. injections of azoxymethane (AOM) (8 mg/ kg). Two other groups were fed the high-fat diet, one for 8 weeks prior to and the other during AOM injections. A 5% fat diet was fed to rats when not on the 30% fat diet and to a control group of 25 animals. High fat diet increased intestinal tumor frequency up to 2-fold when given for at least 4 weeks after but not during or prior to AOM injections; this increase occurred even after a prolonged interval (10 weeks) between the last AOM injection and the high-fat diet. In general, tumor frequency increased according to the length of time animals were fed the high-fat diet after AOM. Therefore, the high-fat diet in this model exhibited most of the properties of promoters developed from murine skin cancer, thus adding support to the concept that excess dietary fat acts at the promotional phase of carcinogenesis.

Animals↗
PubMed1981

Effect of dietary wheat bran and dehydrated citrus fiber on azoxymethane-induced intestinal carcinogenesis in Fischer 344 rats.

The effect of dietary wheat bran and dehydrated citrus fiber on carcinogenesis of the colon and small intestine was studied in male F344 rats. Weanling rats were fed semi-purified diets containing 5% fat and 15% wheat bran or citrus fiber. At 7 weeks of age, all animals, except vehicle-treated controls, received weekly sc injections of 8 mg azoxymethane (AOM)/kg body weight for 10 weeks. The AOM- or vehicle-treated groups were autopsied 20 weeks after the last injection of AOM. The animals fed the wheat bran or citrus fiber diet and treated with AOM had a lower incidence (number of animals with tumors) and multiplicity (number of tumors/tumor-bearing animal) of colon tumors and tumors of the small intestine than did those fed the control diet and treated with AOM. Animals fed the diet containing wheat bran developed fewer adenomas and adenocarcinomas of the colon than did the rats fed the control diet; the number of adenomas but not the number of adenocarcinomas was reduced in rats fed the citrus pulp diet. This study thus indicates that diets containing wheat bran and citrus fiber reduced the risk of intestinal cancer.

Adenocarcinoma↗
PubMed1984

Tumor promotion by dietary fat in azoxymethane-induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat.

The promoting effect of dietary corn oil (CO), safflower oil (SO), olive oil (OO), coconut oil (CC), and medium-chain triglycerides (MCT) on azoxymethane (AOM)-induced colon tumors was studied in female F344 rats. The animals were fed low-fat diets containing 5% CO, 5% SO, or 5% OO 2 weeks before, during, and 1 week after sc injection of 20 mg AOM/kg body weight. One week after the AOM treatment, groups of animals were transferred to high-fat diets containing 23.52% CO, 23.52% SO, 23.52% OO, and 23.52% CC, or 5.88% CO + 17.64% MCT; the remaining animals were continued on 5% fat diets. All animals were fed these diets until the termination of the experiment. Body weights and intakes of calories, protein, and micronutrients were comparable among the various dietary groups. The incidence of colon tumors was increased in rats fed diets containing high-CO and high-SO compared to those fed low-CO and low-SO diets, whereas the diets containing high OO, CC, or MCT had no promoting effect on colon tumor incidence. There was a significant increase in the excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid in animals fed the high-CO and high-SO diets and no difference in these secondary bile acids excretion in animals fed the high-OO and high-CC diets compared to those animals fed their respective 5% fat diets. This study thus indicates that not only the amount of dietary fat but also the fatty acid composition (type) of fat are important factors in the determination of the promoting effect in colon carcinogenesis.

Adenocarcinoma↗
PubMed1984

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Animals↗
PubMed1984

Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats.

The histogenesis of large intestinal carcinomas was studied by use of a low dose (2 mg/kg/wk) of azoxymethane [(AOM) CAS: 25843-45-2] administered im to inbred F344 rats. No evidence of benign polyp was seen, and the carcinomas in this model did arise directly from the flat mucosa. In marked contrast to the standard dose (8 mg/kg/wk) studies, low-dose AOM carcinogenesis yielded the following unusual features: a) There was a very high incidence of readily metastasizing mucinous adenocarcinomas that were extremely aggressive and easily transplantable; b) the carcinomas, microscopic and macroscopic, were localized predominantly in the proximal large intestine; c) foci of atypical early neoplastic (or so-called dysplastic) crypts as well as early carcinomas were frequently associated with the lymphoid aggregates in the intestinal wall; d) Paneth cells were commonly seen to be associated with these atypical crypts and/or early carcinomas associated with the lymphoid aggregates; and e) there was a virtual lack of the dilated, distorted, or hyperdistended crypts in noncarcinomatous epithelia. The significance of the lack of dilated, distorted, hyperdistended crypts and the similarity of this finding with the findings in the low incidence of colon cancer in the Japanese population are discussed.

Animals↗
PubMed1984

Effect of dietary unsaturated and saturated fats on azoxymethane-induced colon carcinogenesis in rats.

The effects of dietary unsaturated and saturated fats on chemically induced colon carcinogenesis were examined in male Donryu rats. The rats were fed two types of semipurified diets consisting of 5% linoleic acid or 4.7% stearic acid plus 0.3% essential fatty acid as dietary fats. The rats were treated with azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and sacrificed 15 weeks after the last injection of the carcinogen. The rats fed unsaturated fat diet demonstrated a significantly higher incidence of colon tumors [100%], more tumors per rat [2.68 +/- 1.60 (S.D.)], and greater malignant differentiation histologically than did those fed saturated fat diet [76%, 1.79 +/- 1.59, respectively]. Lipid analysis of colon tumors and colon mucosa showed that unsaturated fat diet altered the phosphatide fatty acyl composition of colon mucosa markedly and increased the content of arachidonic acid in the neutral lipid of colon tumors. The altered lipid composition of the mucosa may increase the sensitivity of the colon to the carcinogen, and the excess of arachidonic acid or its metabolites may be the primary agents of cocarcinogenesis of colon tumors. These findings suggest that dietary unsaturated fats have potent cocarcinogenic effects on colon carcinogenesis.

Animals↗
PubMed1982

Morphogenesis of colonic carcinoma. Ultrastructural studies of azoxymethane-induced early lesions in colon epithelium of Fischer 344 rats.

Marked dilation and distortion of the crypts have been observed in the colonic epithelium of Fischer-344 rats after four to six weekly doses of azoxymethane (8 mg/kg). These changes precede malignant transformation in this model and, therefore, may be considered premalignant. Ultrastructural morphologic aspects of these crypts can arbitrarily be divided into three stages: an early stage of increased mucus secretion and "exhausted" appearance of mucous cells; an intermediate stage of severe crypt dilation, with extreme thinning of crypt epithelium and neutrophilic emigration to the mucous pool of the crypt lumen; and a late stage characterized by repopulation of the crypts, with epithelial cells showing an increased nuclear-cytoplasmic ratio and bizarre nuclei and nucleoli. The surface epithelium between the crypts shows increased cell loss and alterations of cell membrane. Similar structure of crypts has been described in the mucosa remote from carcinomas in rats and humans, and in various precancerous changes in humans (ie, ulcerative colitis and Crohn's disease). Therefore, I propose that these lesions are significant in human colon carcinogenesis as well.

Animals↗
PubMed1982

Combined inhibitors of carcinogenesis: effect on azoxymethane-induced intestinal cancer in rats.

Outbred male Sprague-Dawley CD rats were fed a complete semisynthetic diet and were given supplemental low doses (2 ppm) of selenium as H2SeO3 in their drinking water or 50 mg 13-cis-retinoic acid (13-cis-RA) and 2 g beta-sitosterol/kg diet either singly, in combinations of two, or in combinations of all three. Intestinal tumors were induced with eight weekly sc injections of 8 mg azoxymethane (AOM)/kg body weight, and inhibition of tumor formation was determined by tumor counts after 26 weeks. Noncarcinogen controls for each dietary group received eight injections of sterile water. Tumor inhibition was statistically significant in 2 groups of animals: Dietary control animals had a tumor frequency of 5.07 tumors/rat, rats receiving selenium- plus 13-cis-RA supplementation had a tumor frequency of 3.77, and those being given the combination of all three inhibitors had 2.75 tumors/rat. Analysis of fecal steroids from 3 AOM groups (dietary controls, the beta-sitosterol plus 13-cis-RA-supplemented group, and the group receiving all three additives) after 4 months of supplementation showed that the addition of beta-sitosterol to the diet had no effect on acidic or neutral steroids, regardless of the observed difference in tumor frequency. These results suggest that subpharmacologic doses of inhibitors, particularly those that inhibit the process by different mechanisms, while ineffective alone, may provide significant inhibition of tumorigenesis when used in combination.

Animals↗
PubMed1982

Effect of beta-glucuronidase inhibitor on azoxymethane-induced colonic carcinogenesis in rats.

In this study of the role of microfloral beta-glucuronidase in colonic carcinogenesis, the effect of beta-glucuronidase inhibitor was evaluated. Starting at 5 weeks of age, male Donryu rats were fed either a semisynthetic diet or the same diet containing 0.1% beta-glucuronidase inhibitor as N-cyclohexyl-5-O-acetyl-2,4-O-p-methoxybenzylidene) -D-glucaro-1-amide-6,3-lactone (C-GAL). All animals were given s.c. injections of 7.4 mg azoxymethane (AOM) per kg body weight once a week for 11 weeks and followed for an additional 20 weeks. Most animals receiving the colonic carcinogen developed tumors in the colon, and a few also developed tumors in the small intestine. However, the number of tumors in the large intestine of the rats given C-GAL at the same time as AOM was significantly lower than in the control rats, especially in the proximal half of the colon, but those given C-GAL after AOM treatment had almost the same number of colon tumors as did the controls. It is concluded that, since bacterial beta-glucuronidase activity in the feces of rats given 0.1% C-GAL was significantly inhibited, intestinal microfloral beta-glucuronidase may play an important role in colonic carcinogenesis caused by AOM.

Animals↗
PubMed1978

Effect of dietary undegraded carrageenan on colon carcinogenesis in F344 rats treated with azoxymethane or methylnitrosourea.

The effect of dietary undegraded carrageenan (Viscarin 402) on colon carcinogenesis was studied in female inbred F344 rats. Weanling rats were fed semipurified diets containing 0 or 15% undegraded carrageenan. At 7 weeks of age, all animals except controls were given azoxymethane (AOM) s.c. at a dose rate of 8 mg/kg body weight per week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose level of 2 mg/rat twice a week for 3 weeks. The AOM groups were autopsied 40 weeks and the MNU groups 30 weeks after the first injection. No tumors were induced in the colon or in other organs of untreated rats fed the control diet. One untreated rat fed the carrageenan diet showed a colon adenoma. The animals fed the carrageenan diet and treated with AOM or MNU had a higher incidence of colorectal tumors (number of rats with colorectal tumors and number of tumors per tumor-bearing rat) than did those fed the control diet and treated similarly. The undegraded carrageenan (Viscarin 402) in the diet had an enhancing effect in colorectal carcinogenesis in rats evoked by AOM or MNU.

Animals↗
PubMed1980

Contrasting effects of subtotal enteric bypass, enterectomy, and colectomy on azoxymethane-induced intestinal carcinogenesis.

Compensatory hyperplasia after extensive loss of functioning small or large intestine might predispose to the development of neoplasia in the residual adapted bowel. To test this hypothesis, male Fischer rats were randomized to receive 85 to 90% jejunoileal resection or bypass, subtotal colectomy, or no operation (controls). One week later, the first of six weekly s.c. injections of azoxymethane (15 mg/kg/week) was given. At the 36th week postoperatively, mean body weight after enterectomy or colectomy it was 78 to 79% of control. Adaptation after all three operations was characterized by 22 to 84% increments in villous height and crypt depth in the residual functioning ileum (p = 0.05 to 0.001); the depth of colonic crypts was unchanged. Fewer rats developed intestinal tumors after enteric bypass (36%) than after any of the other treatments (80 to 91%) (p = 0.01 to 0.001); the depth of colonic crypts was unchanged. Fewer rats developed intestinal tumors after enteric bypass (36%) than after any of the other treatments (80 to 91%) (p = 0.01 to 0.001). Compared with controls, bypass reduced the number of colonic tumors by 77% (p less than 0.001). Although resection did not affect colonic tumor yield, it tripled the incidence of tumors in the duodenum and jejunum (p = 0.025). Colectomy promoted rectal carcinogenesis (p less than 0.05). Anastomotic tumors were commoner after intestinal resection. the lower frequency of tumors after jejunoileal bypass contrasts with enhanced carcinogenesis after enterectomy or colectomy. Profound reduction in body weight may prevent the promotional effect of adaptive hyperplasia.

Adaptation, Physiological↗
PubMed1995

Varying effect of dietary lipids and azoxymethane on early stages of colon carcinogenesis: enumeration of aberrant crypt foci and proliferative indices.

Animal models have been used extensively to study the role of diet in the etiology and prevention of colon cancer. It is recognized that several experimental variables affect disease modulation and outcome. Our objective was to determine whether an interaction between the dose of carcinogen used and dietary factors exist, using aberrant crypt foci (ACF) as a biological end point. Sprague-Dawley male rats were injected with a low or a high dose of azoxymethane (AOM, 5 mg or 20 mg per kg s.c.) or saline (0.2 ml/animal s.c.), and randomly allocated to four diet groups (N = 8/group) 1 week later. Diets varied with respect to type of fat (corn or olive oil) and levels of fat: normal (5 g/100 g) corn or olive oil (CO or OO), or high (23.5 g/100g) corn or olive oil (HCO or HOO). After 8 weeks of dietary treatment animals were injected with colchicine (1 mg/kg). Two and a half hours later they were killed and their colons assessed for number of ACF, number of crypt/focus (crypt multiplicity), and the size of ACF as well as the number of cells in metaphase and their location in the crypt section. The low dose of AOM induced fewer ACF and ACF with higher crypt multiplicity than did the high dose of AOM. Dietary fats exerted a variable effect on ACF, depending on the dose of AOM. In low-dose AOM groups, both CO diets exerted a growth-enhancing effect on ACF compared with OO diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Mechanism of action of chemoprotective ursodeoxycholate in the azoxymethane model of rat colonic carcinogenesis: potential roles of protein kinase C-alpha, -beta II, and -zeta.

Several lines of evidence from our laboratory and others indicate that epigenetic alterations in protein kinase C (PKC) are involved in colonic carcinogenesis in both man and experimental animals. Furthermore, bile salts, known activators of PKC, have also been implicated in colonic tumor development. Recently, however, our laboratory has demonstrated that, whereas dietary cholic acid increased the occurrence of azoxymethane (AOM)-induced rat colonic tumors, ursodeoxycholic acid was associated with a significant protective effect. In the present studies, we therefore examined changes in PKC isoforms that accompanied AOM-induced tumor formation and investigated whether the chemopromotional and/or chemopreventional actions of these supplemental dietary bile salts involved changes in specific isoforms of PKC. Rats treated with vehicle (saline) or AOM and maintained on bile salt unsupplemented or supplemented diets were used to isolate control colonocytes and carcinogen-induced tumors, which were then subjected to subcellular fractionation. The homogenates and subcellular fractions were then probed for individual PKC isoforms by quantitative Western blotting using isoform-specific antibodies. Normal rat colonocytes expressed PKC-alpha, -beta II, -delta, -epilson, and -zeta. AOM, in unsupplemented or cholate-supplemented groups, caused significant down-regulation of PKC-alpha, -delta and -zeta and up-regulation of PKC-beta II, while increasing particulate PKC-alpha, -beta II, and -zeta in carcinogen-induced tumors compared to normal colonocytes. Dietary supplementation with ursodeoxycholic acid, in marked contrast to these groups, prevented the changes in the subcellular distributions of PKC-alpha, -beta II, and -zeta, and preserved the expression of PKC-zeta in AOM-induced tumors. These studies suggest that changes in specific isoforms of PKC (particularly, PKC-alpha, -beta II, -delta, and/or -zeta) are involved in colonic malignant transformation in the AOM model but do not account for the chemopromotional actions of cholic acid in this model. Furthermore, the ability of ursodeoxycholic acid to block AOM-induced increases in particulate PKC-alpha, -beta II, and -zeta, and/or inhibit down-regulation of PKC-zeta, may contribute to the chemopreventive effects of this bile acid.

Animals↗
PubMed1995

1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol, a noncalcemic analogue of 1 alpha,25-dihydroxyvitamin D3, inhibits azoxymethane-induced colonic tumorigenesis.

Vitamin D3 and its metabolites, particularly 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3), have received increasing attention as potential anticarcinogens in the prevention of cancers in a number of organs, including the colon. These agents, however, have the potential to induce hypercalcemia, thus limiting their practical use for these purposes. In the present studies it was, therefore, of interest to determine whether dietary supplementation with 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (RO24-5531), a recently synthesized apparently noncalcemic analogue of 1 alpha,25(OH)2D3, inhibited colon cancer induced by azoxymethane (AOM). Rats were placed on a standard diet or fed this diet with supplemental RO24-5531 (2.5 nmol/kg feed) before and during (initiation arm), or after AOM or vehicle administration (postinitiation arm). After 34 weeks of study, animals in each group were sacrificed, and their colons were removed and examined macroscopically and microscopically for the presence of tumors. At the time of sacrifice, the animals' serum calcium, phosphorus, 25-hydroxyvitamin D3 and 1 alpha,25(OH)2D3 levels were also analyzed. The results of these studies demonstrated that dietary RO24-5531 supplementation during the initiation arm of these experiments significantly reduced (by 70%) the incidence of AOM-induced colonic tumors compared to rats on the standard diet without RO24-5531. Moreover, this dietary regimen abolished the development of adenocarcinomas in this model. Although there was also a trend for dietary RO24-5531 supplementation during the postinitiation arm of this study to reduce the incidence of colon tumors, this did not reach statistical significance (P > 0.05). In addition, neither dietary RO24-5531 supplementation regimen significantly influenced the animals' rates of growth or their serum levels of calcium, phosphorus, or 25-hydroxyvitamin D3. These studies, therefore, demonstrate for the first time that supplemental dietary RO24-5531 is a chemopreventive agent in the AOM model of experimental colonic carcinogenesis. They also suggest that this agent may ultimately prove useful in clinical colon cancer chemopreventive trials.

Animals↗
PubMedDate not supplied

Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats.

The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.

Animals↗
PubMed1995

Chemoprevention of azoxymethane-induced colon carcinogenesis by dietary feeding of S-methyl methane thiosulfonate in male F344 rats.

Modifying effects of dietary exposure of S-methyl methane thiosulfonate (MMTS) isolated from cauliflower Brassica oleracea L. var. botrytis on rat colon carcinogenesis induced by azoxymethane (AOM) and on the expression of cell proliferation biomarkers were investigated in two experiments. In experiment 1, male F344 rats were given three s.c. injections of AOM (15 mg/kg body weight) and fed 100 ppm MMTS for 5 weeks, starting 1 week before the first dose of AOM. The frequency of colonic aberrant crypt foci was determined at 5 weeks after the start. Feeding of 100 ppm MMTS for 5 weeks significantly decreased the number of aberrant crypt foci/colon. Colonic mucosal ornithine decarboxylase activity and the number of silver-stained nucleolar organizer regions per nucleus in colonic epithelium were significantly decreased by MMTS treatment compared with those of AOM alone. In experiment 2, effects of dietary feeding of MMTS at two doses (20 and 100 ppm) during the postinitiation phase on intestinal tumorigenesis initiated with AOM were investigated by using a long-term experiments in male F344 rats. Incidence of intestinal neoplasms of rats fed MMTS-containing diets after AOM exposure were reduced in a dose-dependent manner. Feeding of MMTS during the postinitiation phase decreased the number of aberrant crypt foci/colon, colonic ornithine decarboxylase activity, 5-bromodeoxyuridine-labeling index in colonic epithelium, and polyamine level in blood compared with those of AOM alone. These results suggest that MMTS might be a possible chemopreventive agent for intestinal neoplasia.

Animals↗