Tissue and species specificity of the microsomal metabolism of N-nitrosomethylbenzylamine.
The microsomal activation of N-nitrosomethylbenzylamine (NMBzA) by oxidation at the methylene carbon atom was examined in various organs of a number of species to determine the role of metabolism in the organ-specificity of tumour induction by NMBzA. In Sprague-Dawley rats, NMBzA was metabolized by microsomes from liver, lung and oesophageal mucosa. In Fischer F-344 rats and in rabbits, metabolic activity was present in both liver and oesophageal mucosa, the only tissues studied in those species. In contrast, in Syrian hamsters and in BALB/cBYJ mice, no NMBzA metabolism was detectable in the oesophagus, but it occurred at relatively high rates in liver, lung and kidney. The forestomach mucosa exhibited undetectable levels of activity in all species except the hamster in which it was present at a very low level. In human oesophageal mucosal microsomes from six patients, rates of metabolism of NMBzA were either undetectable or approximately 70 times lower than those in the Sprague-Dawley rats. A comparison of NMBzA metabolism in the different species with the known carcinogenicity of the nitrosamine in rats and rabbits, and our preliminary data on the acute toxicity of NMBzA in hamsters and mice suggests that, in the oesophagus at least, metabolic activation of NMBzA is necessary to elicit its toxic and/or carcinogenic effect. However, in the liver, which in all species has high metabolic activity but which is also resistant to the toxic and carcinogenic effects of NMBzA, other factors besides metabolic activation must be involved.
D000818:Animals; D001547:Benzaldehydes / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009928:Organ Specificity; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001547:Benzaldehydes; D001565:Benzoates; D001592:Benzyl Alcohols; D002273:Carcinogens; D019817:Benzoic Acid; C014707:nitrosobenzylmethylamine; D019905:Benzyl Alcohol; D004128:Dimethylnitrosamine; C032175:benzaldehyde