RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

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Studies on the mechanisms of respiratory tract carcinoma induction by chemical and physical factors, alone or in various combinations, are pursued in the appropriate animal models. Two recently established Syrian golden hamster colonies (inbred 15:16/EHS:CR and outbred Syrian/CR:RGH) are used for intratracheal instillation of carcinogens adsorbed on particulate carriers alone or in combinations, systemic versus topical treatments,a nd combined treatments with carcinogens and cofactors. F-344 rats are also used for studies on mechanisms of silica-indued carcinogenesis and fibrogenesis. Respiratory epithelial tissue responses are characterized by histological, ultrastructural, histochemical and biochemical methods, and by their study in organ and cell culture conditions. Induction of respiratory tract carcinomas by diethylnitrosamine in hamster was found to be much more effective when the carcinogen was administered starting at one day of age than at 4 or 8 weeks, but the induction of tracheal papillomas is not affected by this age factor. Combined exposure protocols have been used to study the effects of N-methylnitro-sourea, benzo[a]pyrene (BP), 3-methylindole and dimethylsulfoxide. Studies on the role of physical factors are continuing, with protocols involving microtrauma, saline and particulate materials. Metabolism of BP was comparatively studies in hamster trachea, bronchi and lung after single or repeated instillation of BP with ferric oxide particles. The target sites for carcinogenesis (trachea and bronchi) showed the highest level of metabolism and of DNA binding. Silica-induced pulmonary epithelial proliferative lesions are studied for their pathogenetic relationship to granulomatous cell reactions, to the role fo reactive oxygen and cellular mediators of inflammation.