Role of the respiratory system in metabolism of N-nitrosamines after simultaneous application of disulfiram.
Subsequent to modification of N-nitrosamine metabolism by disulfiram, mucus-producing cells and Clara cells in the respiratory tract are involved increasingly in detoxification as well as in bioactivation of N-nitroso-N-methylbenzylamine and N-nitrosodibutylamine. Overtaxing of these cells or local concentration of antigenic metabolites leads to cytolytic defects in tracheal, bronchial and bronchiolar epithelium, in addition to toxic degenerative lesions. The resulting continuous stimulation of proliferation leads to basal-cell hyperplasia, squamous-cell metaplasia and squamous papillomas. In areas with insufficient differentiation, due to cell proliferation, there is an increased probability that focal mutation, subsequent to alkylation of purine bases, will be passed from one cell generation to the next, with subsequent formation of tumours in the bronchiolo-alveolar region.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D004221:Disulfiram / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D009602:Nitrosamines / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D009602:Nitrosamines; C012279:dibutylnitrosamine; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine; D004221:Disulfiram