Effect of cigarette smoke on the mutagenic activation of environmental carcinogens by rodent liver

In order to assess the effect of cigarette smoke (CS) on metabolic enzymes, male hamsters and rats were exposed for two weeks to smoke produced in a H amburg type II smoking machine. The livers were then used for Ames liquid i ncubation and western immunoblot assays. Mutagenic activities of seven hete rocyclic amines (HCAs) in Salmonella typhimurium TA98 in the presence of ra t or hamster liver S9 were elevated up to 3.7 times above controls (includi ng sham smoke control). Enhancement of mutagenic activities of PhIP and afl atoxin B-1 was observed only in CS-exposed hamster, whereas no significant alteration of mutagenicity was observed with 2-aminofluorene, benzo[a]pyren e, and 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene in strain TA98 or wi th six N-nitrosodialkylamines in strain TA100. 7,8-Benzoflavone and/or fura fylline considerably inhibited the mutagenic activation of IQ and Trp-P-1 i n the presence of liver S9 from untreated hamsters and sham smoke- or CS-ex posed hamsters and rats, indicating the predominant involvement of hamster cytochrome P450 (CYP) 1A enzymes in the metabolic activation of HCAs. In ad dition, the data suggest that CS-exposure may selectively induce hepatic CY P1A1/1A2 isoforms. Western immunoblot analyses of liver microsomes using an ti-rat CYP antibodies revealed that CS-exposure increased the levels of ham ster CYP1A2 (3.9-fold) and rat CYP1A2 (3.0-fold) and CYP1A1, without signif icant change in the levels of CYP2E1 and CYP2B and 3A isoforms in each spec ies. The presently observed selective induction of HCA activation and CYP i sozymes due to CS supports the idea that CS may contribute to enhancing eff ects on initiation by carcinogens which are metabolically activated by hepa tic CYP1A1/1A2. In conjunction with results observed for smokers, the prese nt findings indicate that the hamster is a good animal for studies with CS, and that cigarette smoking in combination with intake of heating protein-r ich foods as a life style may markedly contribute to the human carcinogenes is by HCAs. (C) 1999 Elsevier Science B.V. All rights reserved.