title: Effect of cigarette smoke on the mutagenic activation of various carcinogens in hamster.
abstract: Male Syrian golden hamsters were exposed for 1 or 2 weeks to smoke produced by commercial non-filter cigarettes for 5 consecutive days in a Hamburg type II smoking machine. Postmitochondrial fractions (S9) prepared from the liver, lungs, and pancreas were used in the Ames liquid incubation assay, in order to assess the effect of cigarette smoke (CS) on the metabolic activation of four groups of procarcinogens. The mutagenic activities of five heterocyclic amines on strain TA98 in the presence of liver S9 mix were induced up to 3.7 times above controls including sham smoke control, while no significant alteration of mutagenicity was observed with 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and benzo[a]pyrene on TA98 or with N-nirosobis(2-oxopropyl)amine (BOP) on TA100. A similar stimulation of metabolic activation was also observed for 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) with S9 from the lungs but not from the pancreas. The mutagenic potential of 11 carcinogens including aflatoxin B1 (AFB1) and two other heterocyclic amines was also examined using liver S9 from male hamsters pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC). The numbers of revertant colonies were much higher (2-20-fold) in the presence of MC-treated liver S9 than in the presence of PB-treated liver S9, except in the case of AFB1 which showed a higher mutagenicity with PB-induced S9. 7,8-Benzoflavone considerably inhibited the activities of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and Trp-P-1 in the presence of either untreated, MC- or CS-treated liver S9, whereas metyrapone was totally lacking this effect, indicating that cytochrome P450(CYP)1A1/1A2 isoforms of hamster liver are predominantly involved in the metabolic activation of these carcinogens. CS exposure of hamsters might selectively induce hepatic CYP1A2 which cannot activate BOP. Consequently, the present findings could explain, in part, the anticarcinogenic effect of CS on BOP-induced pancreatic tumors in hamsters. The findings further support the idea that CS markedly stimulates the metabolic activation of food-derived carcinogens, which may contribute to the overall carcinogenic effects of cigarette smoking.
authors.affiliation: Radioisotope Laboratory, Gifu Pharmaceutical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Iimura
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
authors.forename: A
authors.initials: A
authors.lastname: Nishikawa
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000818:Animals; D002243:Carbolines / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D004790:Enzyme Induction; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002243:Carbolines; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; D010634:Phenobarbital