Disease relevance of AZOXYMETHANE

• Normal human colon mucosal epithelial cells were cultured in vitro and treated with the oncogenic simian DNA virus (SV40) and the chemical carcinogen azoxymethane [1].
• The effects of ad libitum feeding of a chemically defined diet in liquid form on the incidence and histology of colon cancer induced by 10 weekly sc injections of 7.4 mg/kg of azoxymethane [(AOM) CAS: 25843-45-2] were investigated in W-rats [2].
• 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 [3].
• Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats [4].
• Combined inhibitors of carcinogenesis: effect on azoxymethane-induced intestinal cancer in rats [3].

Psychiatry related information on AZOXYMETHANE

• A similar distribution in the upper small bowel in small-bowel carcinomas induced in Fischer and Sprague-Dawley rats by azoxymethane (90-160 mg/kg) suggests defense mechanisms within ileal mucosa [5].
• This study investigated the effects of diet and alcohol consumption on azoxymethane (AOM)-induced liver and gastrointestinal neoplasia in male rats [6].

High impact information on AZOXYMETHANE

• Two weeks later, 30 animals in each group received a subcutaneous injection of azoxymethane (15 mg/kg body weight); 1 week later, they received a second injection [7].
• PURPOSE: The purpose of this study was twofold: 1) to investigate the activity of N-myristoyltransferase in azoxymethane-induced rat colonic cancer tissue compared with normal and normal-appearing rat colonic tissue and 2) to determine if similar differences would be observed in a small sample of human colonic tumors [8].
• Continuous oral administration of DFMO at 1% (approximately 8 mg/g body wt/wk) and 0.25% (approximately 2 mg/g body wt/wk) produced 93% inhibition of ODC induction by AOM in the right and left colons throughout the study [9].
• Interactions of selenium deficiency, vitamin E, polyunsaturated fat, and saturated fat on azoxymethane-induced colon carcinogenesis in male F344 rats [10].
• The clonal composition of neoplastic foci was examined in histological sections of the colonic epithelium of azoxymethane (CAS: 25843-45-2)-treated CBA/Ca----C57BL/6J mouse aggregation chimeras, with the use of H-2 antigens as markers of cellular genotype [11].

Chemical compound and disease context of AZOXYMETHANE

• At 7 weeks of age, all animals except controls were given azoxymethane (AOM) sc at a dose rate of 8 mg/kg body weight/week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose rate of 2 mg/rat twice a week for 3 weeks [12].
• At 7 weeks of age, germ-free and conventional rats were treated with 20 weekly intrarectal 1,2-dimethylhydrazine (20 mg per kg body weight per week) or subcutaneous azoxymethane (10 mg per kg body weight per week) doses and were autopsied 15 weeks later [13].
• In our previous short-term experiment, Citrus auraptene inhibited the development of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions for colorectal carcinoma [14].
• Polyethylene-glycol suppresses colon cancer and causes dose-dependent regression of azoxymethane-induced aberrant crypt foci in rats [15].
• Rat colonic epithelium which had been induced to a premalignant state by the colonic carcinogen azoxymethane was used as a model for patients at high risk of colorectal carcinoma, and the efficacy of dietary DHEA for chemoprotection against tumorigenesis was evaluated [16].

Biological context of AZOXYMETHANE

• CONCLUSIONS: COX-2 but not COX-1 gene expression is markedly elevated in most colonic tumors examined in azoxymethane-treated rodents [17].
• The NAG-1 transgenic mice (NAG-(Tg+)) were characterized, and then the antitumorigenic activity was evaluated with 2 colorectal carcinogenesis models: chemical induction with azoxymethane and genetic induction using the Apc(Min+) mutation [18].
• Although there is a large body of evidence for bile salts as a cocarcinogen in azoxymethane-induced colorectal cancer, bile salt-induced apoptosis of colorectal cancer cells has not yet been studied in detail [19].
• 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 [20].
• Thus, we have demonstrated that loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms, providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor gene in the colon [21].

Anatomical context of AZOXYMETHANE

• The transmission electron microscopic features of grossly normal colonic mucosa in the azoxymethane [(AOM) CAS: 25843-45-2]-treated rat model of colonic carcinogenesis were studied by the method of concomitant variation [22].
• Colon epithelium. II. In vivo studies of colon carcinogenesis. Light microscopic, histochemical, and ultrastructural studies of histogenesis of azoxymethane-induced colon carcinomas in Fischer 344 rats [23].
• Fatty acid content in the feces increased in the animals on the fat diet but was not affected by azoxymethane [24].
• Further analysis of ras-p21 levels in cytosol and plasma membrane revealed that feeding a HFFO diet resulted in increasing accumulation of ras-p21 in cytoplasm with a concomitant decrease in membrane-bound ras-p21 levels as observed in animals sacrificed 12 and 36 weeks after the last AOM injection [25].
• We compared the metabolism of azoxymethane (AOM) and of N-nitrosodimethylamine (NDMA) by liver microsomes obtained from male F344 rats pair-fed for 3 weeks either a control liquid diet or an isocaloric liquid diet containing ethanol at a concentration of 6.6% by volume [26].

Associations of AZOXYMETHANE with other chemical compounds

• Effect of dietary alfalfa, pectin, and wheat bran on azoxymethane-or methylnitrosourea-induced colon carcinogenesis in F344 rats [12].
• The effect of alfalfa, bran, and cellulose on intestinal tumor formation and fecal billary steroid levels was studied in male Sprague-Dawley rats given injections of azoxymethane (AOM) [27].
• 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 [28].
• Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa [29].
• The present study was designed to investigate the chemopreventive action of dietary curcumin on azoxymethane-induced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phospholipase C gamma 1, lipoxygenase, and cyclooxygenase activities in male F344 rats [30].

Gene context of AZOXYMETHANE

• The present study was undertaken to determine if there is differential expression of COX in colonic tumors in azoxymethane-treated rats [17].
• CONCLUSIONS: These results indicate that COX-2 is expressed very early in the pathogenesis of colitis-associated tumors, and that the expression pattern is similar to that seen in tumors from azoxymethane-treated and Min/+ mice [31].
• Administration of 250, 500, or 1000 ppm of a novel selective EP1 antagonist, ONO-8711, in the diet to azoxymethane-treated C57BL/6J mice also resulted in a dose-dependent reduction of ACF formation [32].
• By mating Fabpl(4xat-132) Cre mice with Tgfbr2(flx/flx) mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-beta signaling in vivo on colon cancer formation induced by azoxymethane (AOM) [21].
• METHODS: Heterozygous Cdx2(+/-) mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane [33].

Analytical, diagnostic and therapeutic context of AZOXYMETHANE

• No intestinal tumors were observed in control groups not receiving azoxymethane [34].
• Comparative studies of parallel experimental animal models with the use of high and low doses of azoxymethane support this conclusion [35].
• After injections of azoxymethane, either 85% end-to-side jejunoileal bypass, 85% jejunoileal resection, or sham bypass was performed [36].
• RESULTS: In control rats, azoxymethane-induced tumor incidence in the DC exceeded that in the PC, but tumor volume was greater in the PC than the DC [37].
• At the highest dose of azoxymethane (50 microg/g body weight), factor VIII activity in plasma decreased by 98% within 36 hours after treatment, which was associated with an 80% reduction in hepatic factor VIII messenger RNA (mRNA) [38].

References