Formation of methylnitrosocyanamide from methylguanidine and sodium nitrite in simulated gastric juice and in stomachs of rats: quantitative estimation by a mutagenicity assay.
The formation of methylnitrosocyanamide (MNC), a carcionogenic N-nitroso compound, from methylguanidine (MG) and NaNO2 in simulated gastric juice (SGJ) and in the stomachs of rats was quantitatively investigated. With a reverse mutation assay in which a tester strain of Salmonella typhimurium was used, MNC formation was shown to increase linearly for about 40--60 minutes after the incubation of MG with NaNO2 in SGJ. However, it decreased rapidly thereafter. The initial rate of MNC formation was directly proportional to the initial molar ratio of MG to NaNO2, but the yields of MNC depended only on the amount of MG added and were fairly constant (0.3--0.5% of the initial MG). MNC did not form at a pH above 2.5 or in the presence of 2% casein in SGJ at pH 1.2. It decomposed rapidly in SGJ at pH 1.2 with a half-life of approximately 2 minutes, whereas it was stable in phosphate buffer at pH 7.0. Following concurrent administration of MG and NaNO2 via stomach tube, MNC formation was detected in the pylorus-ligated stomachs of rats preconditioned with a casein-free dextrin diet but not in those of rats preconditioned with a casein-containing or synthetic diet. The yields of MNC observed 40--60 minutes after administration of reactants ranged from 0.02 to 0.05% of the initial MG. The possible environment significance of MNC formation in vivo was considered.
D000818:Animals; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008760:Methylguanidine / Q000378:metabolism*; D009153:Mutagens; D009573:Nitrites / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D012977:Sodium Nitrite / Q000378:metabolism*
D006146:Guanidines; D009153:Mutagens; D009573:Nitrites; D009602:Nitrosamines; C011927:methylnitrosocyanamide; D008760:Methylguanidine; D012977:Sodium Nitrite