Disease relevance of METHYLAZOXYMETHANOL

• Inbred male F344 rats treated with 20 mg methylazoxymethanol (MAM)/kg body weight showed minimal damage to DNA in bone marrow, spleen, and thymus and no suppression of the humoral immune response to human serum albumin (HSA) [1].
• Exocrine pancreatic neoplasms induced by methylazoxymethanol acetate in the guppy Poecilia reticulata [2].
• Liver neoplasms including trabecular hepatoma and cholangioma were induced in medakas (Oryzias latipes) by the addition of methylazoxymethanol acetate to their aquarium water at levels of 0.1-3 ppm for periods ranging from 1 to 120 days [3].
• Leiomyomas and leiomyosarcomas of the kidney in 4-day-old BUF rats given methylazoxymethanol acetate intraperitoneally [4].
• METHODS: Colonic carcinomas were induced in male Sprague-Dawley rats by six weekly intraperitoneal injections of methylazoxymethanol [5].

Psychiatry related information on METHYLAZOXYMETHANOL

• Hyperactivity and instrumental learning deficits in methylazoxymethanol-treated rat offspring [6].
• In the rat, intraperitoneal injection of the anti-mitotic agent methylazoxymethanol (MAM) during intra-uterine development (embryonic day 17) induces cytoarchitectural abnormalities in the hippocampus and the cortex and behavioural changes reminiscent of positive, negative and cognitive symptoms of schizophrenia [7].
• Fixed-ratio (FR) discrimination learning in adult male spontaneously hypertensive rats (SHR), methylazoxymethanol-induced microencephalic Sprague-Dawley (MAM), and Sprague-Dawley control rats was examined [8].
• The sleep-wakefulness cycle and spindle bursts during paradoxical sleep in microencephalic rats induced by prenatal administration of methylazoxymethanol (MAM) acetate [9].

High impact information on METHYLAZOXYMETHANOL

• A single injection of methylazoxymethanol in pregnant rats at 15 days of gestation results in severe cortical atrophy in the offspring [10].
• Methylazoxymethanol treatment of fetal rats results in abnormally dense noradrenergic innervation of neocortex [10].
• Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following a single brief exposure to methylazoxymethanol acetate [(MAM-Ac) CAS: 592-62-1] [2].
• Acute effects of dietary cholic acid and methylazoxymethanol acetate on colon epithelial cell proliferation; metabolism of bile salts and neutral sterols in conventional and germfree SD rats [11].
• Induction of colon tumors in 1,2-dimethylhydrazine-resistant Lobund Wistar rats by methylazoxymethanol acetate [12].

Chemical compound and disease context of METHYLAZOXYMETHANOL

• At 7 weeks of age, all animals except controls were given 1,2-dimethylhydrazine [DMH (150 mg/kg body weight s.c.; one dose)], methylazoxymethanol acetate [MAM acetate (35 mg/kg body weight i.p.; one dose)], or methylnitrosourea (2.5 mg/rat/week intrarectally; two doses), and autopsied 35 weeks later [13].
• The common conditions required for activation of nonmutagenic methylazoxymethanol conjugates, the glucoside cycasin and methylazoxymethyl-beta-D-glucosiduronic acid, are 90-min preincubation at 30 degrees, pH 6.5, with an appropriate hydrolase and Salmonella typhimurium HisG46 [14].
• The oxidation product is methylazoxymethanol-beta-D-glucosiduronic acid because, when hydrolyzed with Escherichia coli beta-glucuronidase, it produced methylazoxymethanol and glucuronic acid and also indicated retention of the beta-linkage of cycasin [15].
• In this study, mutations in the region corresponding to N-terminal phosphorylation sites (codons 1-51) of the rat Ctnnb1 gene were investigated in 20 colon tumors associated with ulcerative colitis and induced with methylazoxymethanol acetate and 1-hydroxyanthraquinone [16].
• Administration of the dopamine receptor stimulant, apomorphine, or the receptor blocker, haloperidol, produced less stereotypy and catalepsy, respectively, in rats lesioned with methylazoxymethanol, compared to controls [17].

Biological context of METHYLAZOXYMETHANOL

• Apoptosis (cell death) induced in mouse bowel by 1,2-dimethylhydrazine, methylazoxymethanol acetate, and gamma-rays [18].
• In contrast to x-ray damage, the extensive death of cerebellar granule cells induced by methylazoxymethanol was found to be independent of the DNA fragmentation characteristic of apoptosis, and was also independent of expression of p53 [19].
• Effects of chronic dietary ethanol on in vivo and in vitro metabolism of methylazoxymethanol and on methylazoxymethanol-induced DNA methylation in rat colon and liver [20].
• Methylazoxymethanol acetate-induced apoptosis in the external granule cell layer of the developing cerebellum of the rat is associated with strong c-Jun expression and formation of high molecular weight c-Jun complexes [21].
• Effects of fetal methylazoxymethanol acetate lesion on the synaptic neurochemistry of the adult rat striatum [22].

Anatomical context of METHYLAZOXYMETHANOL

• These results show that a single dose of methylazoxymethanol acetate can affect almost all hepatocytes and that latent effects persist for long periods of time [23].
• Fatty acid-stimulated oxidation of methylazoxymethanol by rat colonic mucosa [24].
• Methylazoxymethanol is a potent carcinogen and induces tumors predominantly of the small intestine and colon following a single injection [25].
• Previous work has shown that single injections of methylazoxymethanol acetate in rats induce tumors predominantly in the colon, occasionally in the duodenum, and rarely in the jejunum and ileum [26].
• GABAA receptors reorganize when layer 4 in ferret somatosensory cortex is disrupted by methylazoxymethanol (MAM) [27].

Associations of METHYLAZOXYMETHANOL with other chemical compounds

• Such cells were transformed by treatment with methylazoxymethanol acetate; they then exhibited an irregular, piling growth pattern, acquired the ability to grow in soft agar, and thereafter grew as tumors in hamsters given cortisone and in nude mice [28].
• The present study examined fatty acid-initiated metabolism of methylazoxymethanol (MAM) to formaldehyde (HCHO) by the 10,000 X g soluble fraction of rat colonic mucosa, and the role of prostaglandin synthase and lipoxygenase activities in mediating this process [24].
• Previous studies have shown that methylazoxymethanol acetate (MAM) and methylazoxymethanol glucoside (cycasin) cause destruction of differentiation cells in the postnatal mouse cerebellum [29].
• To better understand the biology of the cells comprising the hepatic stroma, livers from medaka (Oryzias latipes) experimentally induced by diethylnitrosamine or methylazoxymethanol acetate were labeled with keratin, actin, and desmin antibodies [30].
• The effect of dietary magnesium hydroxide on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in male F344 rats [31].

Gene context of METHYLAZOXYMETHANOL

• No involvement of APC gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate [32].
• Bcl-2 and Bax expression following methylazoxymethanol acetate-induced apoptosis in the external granule cell layer of the developing rat cerebellum [33].
• Elevated amniotic AVP levels were found in the methylazoxymethanol-treated and undernourished rats, partly concomitant with smaller amount of amniotic fluid [34].
• The data indicate that intestinal and colonic alcohol dehydrogenase plays a role in the tumorigenic effects of methylazoxymethanol and that other non-pyrazole-sensitive enzymes exist in other organs that can also activate this carcinogen [25].
• Non-alcohol dehydrogenase-mediated metabolism of methylazoxymethanol in the deer mouse, Peromyscus maniculatus [35].

Analytical, diagnostic and therapeutic context of METHYLAZOXYMETHANOL

• Induction of hepatic tumors in a teleost (Oryzias latipes) after treatment with methylazoxymethanol acetate: brief communication [3].
• Effect of colostomy on intestinal carcinogenesis by methylazoxymethanol acetate in rats [36].
• Megalocytosis and other abnormalities expressed during proliferation in regenerating liver of rats treated with methylazoxymethanol acetate prior to partial hepatectomy [23].
• To ascertain the role of PKC in regulating APP metabolism in vivo, we used an animal model (methylazoxymethanol-treated rats; MAM rats) in which PKC is permanently hyperactivated in selected brain areas, i.e., cortex and hippocampus [37].
• Alteration of mouse cerebellar circuits following methylazoxymethanol treatment during development: immunohistochemistry of GABAergic elements and electron microscopic study [38].

References