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PubMed2004

Effects of adlay on azoxymethane-induced colon carcinogenesis in rats.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop used in traditional Chinese medicine and as a nutritious food. It has been reported that adlay has anti-inflammatory and anti-tumor activity. Cyclooxygenase-2 (COX-2) is an inducible enzyme functionally related to both inflammation and colon carcinogenesis and is the target of many chemopreventive agents. This study investigated the effect of adlay on colon carcinogenesis and COX-2 expression. In a short-term experiment, male F344 rats were fed diets containing different doses of dehulled adlay and received the colon-specific carcinogen, azoxymethane (AOM), by intraperitoneal injection. All rats were killed after 5 weeks of feeding, and the colons were examined for the preneoplastic lesion, aberrant crypt foci (ACF). Dietary dehulled adlay at levels of 10%, 20%, or 40% significantly reduced the numbers of ACF and aberrant crypts. Dehulled adlay reduced the number of ACF of different sizes but did not affect the crypt multiplicity. Most ACF were found in the middle and distal colons; dehulled adlay significantly suppressed the formation of ACF in the middle colon. In a long-term experiment, male F344 rats were fed diets containing different doses of dehulled adlay and injected with AOM. All rats were killed after 52 weeks of feeding, and colons were examined for tumors and COX-2 protein expression. The results indicated that dehulled adlay did not inhibit colon tumors in spite of a slight suppressing effect in the proximal colon. Rats fed diets containing 20% dehulled adlay had less COX-2 protein expression in both proximal and distal colon tumors. The inconsistent effects between COX-2 protein expression and tumor outcome may be due to regional differences in the colon and the malignancy of the tumors. These findings suggest that dehulled adlay suppresses early events in colon carcinogenesis but not the formation of tumors.

Animals↗
PubMed2004

Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats.

Effects of the water extract of Centella asiatica Linn. on formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and intestinal tumorigenesis in male F344 rats were investigated. Treatment with the extract significantly decreased the number of larger ACF (with four or more crypts per focus) in the large intestine in the early stage, while the number of methylated DNA adducts was not decreased compared with that in the AOM-treated group. In the post-initiation stage, the extract significantly decreased the total number of ACF and the number of larger ACF, accompanied by a decrease in the 5-bromo-2'-deoxyuridine-labeling index and an increase in the induction of apoptotic cells in the colonic mucosa. The incidences of neoplasms, the numbers of adenocarcinomas in the small intestines and entire intestines, and sizes of neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of 10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in the small intestine (p < 0.05). These results suggest that inhibition of the formation of AOM-induced ACF by C. asiatica extract is associated with modification of cell proliferation and induction of apoptosis in colonic crypts and that the extract has a chemopreventive effect on colon tumorigenesis.

Animals↗
PubMed2006

Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Red palm oil (RPO) contains significant levels of carotenoids and Vitamin E. In this experiment we compared the inhibitory effects of RPO (7% and 14% levels) and soybean oil (7% and 14%) on azoxymethane (AOM) induced aberrant crypt foci (ACF). Thirty-two male Fisher 344 rats were randomly assigned to four groups. Two groups received AIN-93 G control (C) diet containing 7% and 14% soybean oil (SBO), respectively. Groups 3 and 4 received a treatment diet consisting of 7% and 14% RPO, respectively. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at 7 and 8 weeks of age. At 17 weeks of age rats were killed by CO(2) asphyxiation. Numbers of ACF (mean+/-SE) in the proximal and distal colon were: 39.9 +/- 0.9, 53.8 +/- 2.8, 26.0 +/- 3.0, 27.5 +/- 1.5 and 118.2 +/- 1.7, 125.6 +/- 3.2, 41 +/- 7, 52.3 +/- 1.8 in rats fed 7% SBO, 14% SBO, 7% RPO and 14% RPO, respectively. The results of this study showed that RPO reduced the incidence of AOM induced ACF and may therefore have a beneficial effect in reducing the incidence of colon cancer.

Animals↗
PubMed2006

Enhanced estrogenic responses and sensitivity to azoxymethane following dietary soy isoflavone supplementation in older female rats.

Soy isoflavones are popular supplements among middle-aged and older women based on their potential protection against cancer and their use as alternative hormone replacement therapy. The purpose of this study was to investigate the effects of dietary soy isoflavones on early stage colon cancer in various ages of female rats. Young (1month), mature (11month) and old (22month) female Fisher 344 rats were fed either the control diet or a diet containing 0.4% soy isoflavone isolate for 1week, injected once with 20mg/kg azoxymethane (AOM) and maintained on the diets for another 15weeks. The concentration of isoflavones in the diet was 2g/kgdiet, composed of 1.2g/kg genistin, 0.7g/kg daidzin and 0.1g/kg other isoflavones including glycitin, acetylgenistin, acetyldaidzin, genistein, daidzein, and glycitein. There was no difference over all ages in the development of preneoplastic colonic aberrant crypt foci between rats fed the soy compared to the control diet, indicating that the soy diet did not provide protection against early stage colonic carcinogenesis. On the contrary, several adverse effects of soy supplementation in female AOM-treated rats were observed. Soy-supplemented rats had greater weight loss and a slower recovery of body weight following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the soy supplement died before the end of the experiment while all animals on the control diet survived to term. The density of normal crypts lining the colonic mucosa was reduced in rats fed the soy compared to control diet, indicating gastrointestinal damage. Uterine weights, serum estradiol and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. These adverse effects of soy isoflavones in aged female animals need further examination because women, and particularly older women, are the prime target population for consumption of soy supplements.

Aging↗
PubMed2005

Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats.

We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague-Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis.

Animals↗
PubMed2006

Noninvasive monitoring of colonic carcinogenesis: feasibility of [(18)F]FDG-PET in the azoxymethane model.

BACKGROUND: Azoxymethane (AOM) is a potent carcinogen that induces colorectal cancer and adenomas in rats. [(18)F]FDG-PET is a molecular imaging technique that is based on the elevated uptake and retention of radiolabeled glucose. At present, it is unknown at which stage FDG accumulation occurs during the adenoma carcinoma sequence. To address this issue, we studied the FDG uptake in AOM-induced rat colorectal adenocarcinoma (CRC) and correlated this with histopathological findings. METHODS: Seventy Fischer 344 rats were injected with AOM. Terminal autopsy took place 20-38 weeks after the first AOM injection. After [(18)F]FDG PET scanning, the rats were sacrificed, tissue [(18)F]FDG uptake was measured, followed by histopathological examination. RESULTS: Macroscopic examination revealed 21 tumors (7 located in the small bowel and 14 in the colon) in 19 rats. On histological examination, we found 10 colonic adenocarcinomas (the first being observed at Week 22) and 7 adenocarcinoma in the small bowel. In total, seven colon adenomas were found in five rats, six of which expressed high-grade dysplasia. The [(18)F]FDG accumulation in small intestine carcinomas was well beyond background accumulation (P<.0001). On PET scanning, two rats showed focal accumulation of the abdominal area, corresponding to small intestine carcinomas. CONCLUSION: Adenocarcinomas had a significantly higher [(18)F]FDG uptake than background bowel uptake. [(18)F]FDG uptake was lower in adenomas than in carcinomas. These data suggest that the AOM model allows the evaluation of intervention strategies with [(18)F]FDG uptake as a valid outcome measure.

Adenocarcinoma↗
PubMed2005

Senna and the formation of aberrant crypt foci and tumors in rats treated with azoxymethane.

Chronic use of anthraquinone laxatives has been blamed for the induction of habituation and the development of colonic cancer, but there are no definitive studies which have demonstrated this. To evaluate the carcinogenic potential of anthraquinones, the effect of long-term senna pod extract (SE) treatment on either healthy rats or rats treated with an initiating tumor agent (azoxymethane--AOM) has been studied. SE (30 and 60mg/kg), administered for 110 weeks, did not induce the development of aberrant crypt foci (ACF) and tumors in healthy rats. The development of ACF and tumors in rats treated with AOM were significantly reduced by SE (30 and 60 mg/kg). These results suggest that a chronic SE use does not predispose to colon cancer. By contrast, SE might exert an anti-tumoral activity on rat colon carcinogenesis.

Adenocarcinoma↗
PubMed2006

Novel mucilage fraction of Sinapis alba L. (mustard) reduces azoxymethane-induced colonic aberrant crypt foci formation in F344 and Zucker obese rats.

Seeds of Sinapis alba Linn. (commonly called yellow or white mustard) and their components have been reported to possess anticancer properties. In this study, we evaluated the efficacy of a novel mucilaginous fraction of mustard seeds in inhibiting colonic preneoplastic changes in animal models of sporadic and obesity-associated colon cancer. In two separate studies, male Sprague-Dawley or female Zucker obese rats, injected with azoxymethane (15 or 10 mg/kg body wt. once a week for 2 weeks, respectively), were fed AIN-93G diets with or without 5% mustard mucilage (MM) (w/w) for 8 weeks. Our aim was to measure the ability to modulate the number of aberrant crypt foci (ACF), putative preneoplastic lesions of the colon. The data were classified into total numbers of ACF and large ACF (crypt multiplicity of 4 or more). We report here that 5% MM significantly (p<0.05) decreased the number of total (approximately 21% inhibition) and large (approximately 50% inhibition) ACF in the colons of Sprague-Dawley rats compared to that in untreated controls. In addition, 5% MM supplemented diet significantly lowered (p<0.05) the number of total (approximately 63% inhibition) and large (approximately 60% inhibition) colonic ACF in Zucker obese rats compared to untreated obese rats, and had no effect on fasting plasma cholesterol or triglyceride levels. These results demonstrate the possible role of MM as a functional food against sporadic and obesity-associated colon cancer, and provide impetus to conduct research to understand the underlying mechanism(s) of action.

Adhesives↗
PubMed2000

The effects of N-methyl-N-nitrosourea and azoxymethane on focal cerebral infarction and the expression of p53, p21 proteins.

If the activity of pro-apoptotic genes can be down-regulated by certain chemicals, cells may be protected from apoptosis. To test this hypothesis in a cerebral infarction model, we used N-methyl-N-nitrosourea (MNU) and azoxymethane (AOM), which were approved gene-modulating chemicals. A focal cerebral infarction was created by coagulation of the right middle cerebral artery and ipsilateral common carotid artery (CCA) and simultaneous transient occlusion of the contralateral CCA for 30 min in 25 adult Sprague-Dawley rats that were sacrificed 24 h later. In one group (n=7), MNU (5 mg/kg) was injected intravenously 30 min before initiation of ischemia. In another group (n=7), AOM (15 mg/kg) was administered intraperitoneally before 24 h of ischemia. The infarction volumes were checked and the brains were stained for p53 and p21 proteins. The width in micrometers of the peri-infarct area containing p53 or p21 protein-positive cells, and the number of p53 or p21 protein-positive cells (cells/HPF) were measured at an adjacent peri-infarct area. The AOM-treated group showed a significantly reduced infarction volume (by 42.5%, p<0.001), a significantly greater number of p53 positive cells (by 12.0%, p<0. 05), and a significantly wider p53 protein-positive area (by 15.6%, p<0.01) than the untreated group. AOM did not show any influence on the expression pattern of the p21 protein. MNU had no effect in the expression of p53 or p21 proteins. As a result, we concluded that AOM revealed a protective effect in ischemia by suppressing the pro-apoptotic activity of the p53 gene. Safer chemicals that can modulate apoptotic genes, if any, will provide a new therapeutic modality for cerebral infarction.

Animals↗
PubMed1999

Quantitative assessment of azoxymethane-induced aberrant crypt foci in inbred mice.

Heritable differences in tumor susceptibility are observed in mice after repetitive exposures to the organotropic colon carcinogen azoxymethane (AOM). The following study was undertaken to determine whether early morphological alterations within the colonic epithelium correlate with subsequent cancer risk. A/J and SWR/J (susceptible) and AKR/J (resistant) mice were injected once a week with AOM at a dose of 10 mg/kg, i.p., for a total of 6 weeks. Four weeks after the last injection, methylene blue-stained whole-mount colons were examined for the presence of colonic epithelial lesions referred to as aberrant crypt foci (ACF). Putative lesions identified under low magnification were further characterized by H&E staining of corresponding sections. AOM produced a treatment-related increase in ACFs in each of the mouse lines examined. The tumor-susceptible SWR/J and A/J mice developed on average between three- and sixfold more ACFs in the distal colon (32 and 15/cm of colon, respectively) than the resistant AKR/J mice (5/cm colon). The size distribution of ACFs was further analyzed in each of the strains. In SWR/J and A/J, 20-35% of lesions were classified as large ACFs, consisting of 5 or more aberrant crypts per focus. This is in striking contrast to the size distribution of lesions identified in the AKR/J colons, where fewer than 5% of grossly identified lesions were classified as large. In fact, the majority (> 80%) of ACFs in AKR/J mice consisted of only 1-2 aberrant crypts@focus. In addition, there was no evidence of dysplasia in any of the AKR/J lesions examined, whereas the lesions in susceptible mice were dysplastic (adenomas). Our data indicate that tumorigenic response is associated with the extent and multiplicity of ACFs that form within the colonic epithelium at an early time point after carcinogen exposure. These studies further support the use of this morphological biomarker as a short-term endpoint of colon tumorigenesis.

Animals↗
PubMed1998

Expression of G protein alpha subunits in normal rat colon and in azoxymethane-induced colonic neoplasms.

BACKGROUND & AIMS: Heterotrimeric G proteins are important in growth-regulating signal transduction. The aim of this study was to characterize the relative expression of G protein alpha subunits in rat colonocytes, colonocyte antipodal plasma membranes, and colonic neoplasms. METHODS: Antipodal plasma membranes were prepared from isolated colonocytes. Azoxymethane was administered to rats to induce colonic neoplasms. K-ras mutations in the neoplasms were determined by oligonucleotide hybridization and confirmed by primer mediated-restriction fragment length polymorphism. Colonocyte and tumor homogenates or membranes were probed for Galpha subunits by Western blotting with isoform-specific antibodies. RESULTS: The expressions of Galphai2, alphai3, and alphaq/11 were significantly enriched in the basolateral compared with brush border fraction of colonic antipodal plasma membranes. In neoplasms without K-ras mutations, the expression of Galphai2 increased 4-fold, Galphas(long) increased 2.5-fold, and Galphai3 increased 1.5-2-fold. Expression did not differ among tumor grades. K-ras mutations were associated with lowered expression of G proteins, especially Galphao. CONCLUSIONS: In colonocytes, Galpha subunits are localized primarily in basolateral plasma membranes. The increased expressions of Galphai2 and, to a lesser degree, Galphai3 and Galphas(long) in tumors was independent of tumor grade but was modulated by the presence of K-ras mutations.

Animals↗
PubMed1991

Hepatic pathology of the colon carcinogen, azoxymethane, in Hanford-Moore miniature pigs.

Azoxymethane (AOM) is commonly used in colon carcinogenesis studies in rodents. In an attempt to develop a large animal model of human colon cancer, AOM was given to Hanford-Moore miniature pigs. Six pigs were injected intraperitoneally with a single dose of AOM of either 5, 10, 20, 40 or 55 mg per kg body weight. Within 48 h, severe signs of toxicity and death occurred in animals receiving greater than 20 mg per kg AOM. After 30 days, all surviving animals were killed and necropsied. Acute hepatic necrosis with haemorrhage was the major toxic effect of AOM in all animals receiving doses exceeding 20 mg per kg. In a second, longer-term experiment, eight pigs were injected with either 20 mg per kg AOM weekly or 10 mg per kg AOM every other week or a combination of both treatments. Chronic toxic effects were limited to the liver. No colon tumours were observed. It is concluded that this particular species demonstrates marked hepatic sensitivity to the toxic effects of AOM.

Animals↗
PubMed2001

Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats.

The modifying effects of dietary feeding of a polymethoxyflavonoid nobiletin isolated from Citrus unshiu on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of nobiletin on cell proliferation activity of ACF using a monoclonal antibody MIB-5. Rats were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01% or 0.05% nobiletin for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 139 +/- 35 ACF/rat at the end of the study (week 5). Dietary administration of nobiletin caused significant reduction in the frequency of ACF: 70 +/- 15 (50% reduction, p<0.001) at a dose of 0.01% and 63 +/- 10 (55% reduction, p<0.001) at a dose of 0.05%. Nobiletin feeding significantly lowered MIB-5-index in ACF. Also, dietary administration of nobiletin significantly reduced prostaglandin E2 content in the colonic mucosa. These findings might suggest possible chemopreventive ability of nobiletin, through suppression of cell proliferating activity of ACF, in the development of ACF.

Administration, Oral↗
PubMed2001

Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiber zerumbet.

The modifying effects of dietary feeding of zerumbone isolated from Zingiber zerumbet on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed. In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei. To induce ACF rats were given three weekly subcutaneous injections of AOM (15 mg/kg body weight). They were also fed the experimental diet containing 0.01% or 0.05% zerumbone for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 84+/-13 ACF/rat at the end of the study (week 5). Dietary administration of zerumbone caused reduction in the frequency of ACF: 72+/-17 (14% reduction) at a dose of 0.01% and 45+/-18 (46% reduction, p<0.001) at a dose of 0.05%. Feeding of zerumbone significantly reduced expression of COX-2 and prostaglandins in colonic mucosa. Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei. These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF.

Animals↗
PubMedDate not supplied

Antimutagenicity of sodium selenite in Chinese hamster V79 cells exposed to azoxymethane, methylmethansulphonate and hydrogen peroxide.

In the last 10 years, there is an increasing interest in selenium (Se) because of its environmental, biological, and toxicological importance, and in particular, because of its antioxidant properties. However, inspite of extensive studies, the optimal concentration of Se to be used for its beneficial effects in not yet known. In addition, the mechanisms of Se antioxidant property require further study. We report on the effects of various mutagens/carcinogens such as azoxymethane, methylmethanesulphonate, and hydrogen peroxide on Chinese V79 hamster cells, in presence of sodium selenite in the concentration of 0.5 microM. We found that Se reduced the genotoxic effect of these mutagens/carcinogens. We also investigated enzymatic activities of glutathione peroxidase, catalase, superoxide dismutase, and glutathione S-transferase, in order to understand the Se involvement in the detoxification of free radicals. Sodium selenite increased the activities of glutathione peroxidase and catalase.

Animals↗
PubMed1997

Phenobarbital and 3-methylcholanthrene treatment alters phase I and II enzymes and the sensitivity of the rat colon to the carcinogenic activity of azoxymethane.

It has been hypothesized that cancer risk may be influenced by phase I and II drug-metabolizing enzyme systems. This study attempted to determine the relationship between colon phase I and II enzyme activity and the subsequent induction of aberrant crypt foci (ACF), preneoplastic lesions by azoxymethane (AOM), a colon-specific carcinogen. Phenobarbital (PB) and 3-methylcholanthrene (MC) treatment (prototype hepatic inducers of phase I and II enzymes) provided the framework to study the induction of phase I and II enzymes in the rat colonic mucosa. Following induction for five consecutive days, the animals were given a single injection of AOM. Phase I and II enzymes were determined fluorometrically and spectrophotometrically and ACF were identified microscopically. Phase I and II xenobiotic metabolizing enzymes were induced in the rat colonic mucosa by prototype hepatic inducers. A lower number of ACF and crypt multiplicity was observed in animals induced with MC than in those in the non-induced and PB groups. Altered levels of phase I and II enzymes in the colon during preinitiation stages were associated with modulation in the growth of ACF, putative preneoplastic lesions.

Animals↗
PubMed1999

Effects of roselle (Hibiscus sabdariffa Linn.), a Thai medicinal plant, on the mutagenicity of various known mutagens in Salmonella typhimurium and on formation of aberrant crypt foci induced by the colon carcinogens azoxymethane and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in F344 rats.

The 80% ethanol extract of roselle (Hibiscus sabdariffa Linn.), a medicinal plant in Thailand, was examined for antimutagenic and chemopreventive activity in a colon carcinogenesis model. It reduced about 60-90% of the mutagenicity induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and other heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MelQ),2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline(MelQx),3-amino-1,4-dimet hyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2),2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1),2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), at a concentration of 12.5 mg/plate in the Salmonella mutation assay. The extract showed no mutagenicity and no antibacterial activity below this dose. Mutagenicity of methylazoxymethanol (MAM) acetate, which, like PhIP, is a colon carcinogen,was also efficiently inhibited by the roselle extract. To investigate chemoprevention by roselle in a colon carcinogenesis model, we examined the inhibitory effects of the roselle extract in F344 rats in which aberrant crypt focus (ACF) formation was induced by azoxymethane (AOM) and PhIP. In the initiation stage, the number of AOM-induced ACF in the colon was significantly decreased by roselle (17-25%) compared with that in rats treated with AOM alone. The amount of O6-methylguanine in the colonic mucosa tended to be decreased in the roselle-treated rats. The number of PhIP-induced ACF was also significantly decreased by roselle treatment (22%) at a concentration of 1.0 g/kg body weight in the initiation stage. However, in the post-initiation stage of AOM-induced ACF formation, roselle increased the number of ACF, especially the number of foci which had more than three crypts/focus. These results indicate that roselle has antimutagenic activity against MAM acetate and heterocyclic amines and that it decreases the number of AOM- and PhIP-induced ACF in the initiation stage, although it rather increased the number of ACF in the post-initiation stage.

Animals↗
PubMed2000

Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.

The present study is part of a program to obtain effective chemopreventive agents with low toxicity from medicinal herbs and traditional herbal medicines. We previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix) inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the present investigation, we found Sanshishi (Gardeniae fructus) and the traditional herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively. Adverse effects, evidenced by body weight loss, were weaker with OGT than component herbs. To investigate their mechanisms of action, the influence on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied. Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably contributing to their suppressive effects on ACF development. The results suggest that OGT may be useful for colon cancer chemoprevention in terms of efficacy and toxicity.

Animals↗