Bürkle V, Wittenberg H, Schweinsberg F, Weissenberger I, Schweinsberg E, Brückner B
IARC Sci Publ. 1984(57):533-41.
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.
在双硫仑改变N-亚硝胺代谢之后，呼吸道中的黏液分泌细胞和克拉拉细胞越来越多地参与N-亚硝基-N-甲基苄胺和N-亚硝基二丁胺的解毒以及生物活化过程。这些细胞的过度负担或抗原性代谢产物的局部浓度升高，除了导致毒性退行性病变外，还会导致气管、支气管和细支气管上皮细胞的溶细胞缺陷。由此产生的持续增殖刺激会导致基底细胞增生、鳞状化生和鳞状乳头瘤。在分化不足的区域，由于细胞增殖，嘌呤碱基烷基化后发生局灶性突变并从一代细胞传递到下一代的可能性增加，随后在细支气管肺泡区域形成肿瘤。
