Mechanistic studies of tobacco carcinogenesis in mouse epidermis and lung tissues.
The particulate matter of tobacco smoke induces benign and malignant tumors in various animal tissues and species. The most widely used bioassay system for evaluating the carcinogenicity of tobacco tars is mouse skin. Mouse skin bioassays have led to the identification of the PAHs as the major tumor initiators, while showing that catechols are important cocarcinogens in tobacco smoke. Mechanistic studies suggest that catechol affects BaP metabolism and especially secondary oxidation reactions of this carcinogen and thus changes the proportion of BPDE-DNA adducts. Comparison of the disposition and metabolism of BaP and its ultimate carcinogenic derivative, anti-BPDE, in mouse epidermis demonstrates that the lower activity of BPDE relative to BaP in mouse skin is partially due to differences in penetration and trapping of BPDE within the epidermis, where it is protected from hydrolysis and reaction with intracellular macromolecules. Although screening for tumorigenicity on mouse skin is limited to the detection of certain classes of carcinogens and is not helpful for the evaluation of organ-specific carcinogens, mouse skin assays of cigarette smoke condensates have nevertheless served as valuable indicators of the tumorigenic potential of tobacco smoke for epithelial tissues.
Melikian
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AA
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
Hecht
S S
SS
Hoffmann
D
D
D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002273:Carcinogens; D002396:Catechols / Q000633:toxicity; D006224:Cricetinae; D004249:DNA Damage; D004817:Epidermis / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008647:Mesocricetus; D051379:Mice; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D002273:Carcinogens; D002396:Catechols; D001564:Benzo(a)pyrene