Biological activity of tobacco smoke and tobacco smoke-related chemicals.
Exposure to whole cigarette smoke from reference cigarettes results in the prompt (peak activity is 6 hrs), but fairly weak (similar to 2 fold), induction of murine pulmonary microsomal monooxygenase activity. This activity can be detected by using as substrates either benzo(a)pyrene or ethoxyresorufin, and can be inhibited by treatment with cycloheximide or actinomycin D. Unlike the induction of pulmonary monooxygenases following intratracheal administration of 3-methylcholanthrene, these cigarette smoke-induced increases were not unequivocally linked to the Ah locus. Whole smoke condensate and fractions derived from these condensates can; a) induce pulmonary monooxygenase activity, b) inhibit benzo(a)pyrene metabolism in vitro, c) be metabolized to forms mutagenic to Salmonella typhimurium tester strains TA153, or TA98, d) transform C3H 10T1/2 cells in vitro, and e) enhance the carcinogenicity of benzo(a)pyrene in murine pulmonary tissue. A potentially important observation is that whereas hepatic tissue is capable of activating whole cigarette smoke condensate to mutagenic forms in vitro, murine pulmonary tissue does not seem capable of such activation. Although these pulmonary-derived tissue homogenates have significant AHH activity and can metabolize Aflatoxin B1, 2-aminofluorene and 7, 8-dihydro-7,8-dihydroxybenzo(a)pyrene to mutagenic forms, these homogenates fail to activate both cigarette smoke condensate and the pro-mutagen, 6-aminochrysene. These results are discussed with reference to the concept that whole cigarette smoke may be both a potential "initiator" and "promotor" of lung cancer in mice, and that this latter property may be the most important in determining cancer risk.
D000818:Animals; D002273:Carcinogens; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000201:enzymology; D009153:Mutagens; D010947:Plants, Toxic; D051381:Rats; D012475:Salmonella / Q000187:drug effects; D012907:Smoking; D014026:Nicotiana
D002273:Carcinogens; D009153:Mutagens; D003609:Dactinomycin; D008748:Methylcholanthrene; D003513:Cycloheximide