EFFECT OF CIGARETTE-SMOKE ON THE MUTAGENIC ACTIVATION OF VARIOUS CARCINOGENS IN HAMSTER

Male Syrian golden hamsters were exposed for 1 or 2 weeks to smoke pro duced by commercial non-filter cigarettes for 5 consecutive days in a Hamburg type II smoking machine. Postmitochondrial fractions (S9) prep ared 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 mu tagenic activities df five heterocyclic amines on strain TA98 in the p resence of liver S9 mix were induced up to 3.7 times above controls in cluding sham smoke control, while no significant alteration of mutagen icity was observed with. 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenze ne and benzo[a]pyrene on TA98 or with N-nirosobis(2-oxopropyl)amine (B OP) on TA100. A similar stimulation of metabolic activation was also o bserved 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 B-1 (AFB(1)) and two other heter ocyclic amines was also examined using liver S9 from male hamsters pre treated with phenobarbital (PB) or 3-methylcholanthrene (MC). The numb ers 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, e xcept in the case of AFB, which showed a higher mutagenicity with PB-i nduced S9. 7,8-Benzoflavone considerably inhibited the activities of 2 -amino-3-methylimidazo[4,5-f]quinoline (IQ) and Trp-P-l in the presenc e of either untreated, MC- or CS-treated liver S9, whereas metyrapone was totally lacking this effect, indicating that cytochrome P450(CYP)1 A1/1A2 isoforms of hamster liver are predominantly involved in the met abolic activation of these carcinogens. CS exposure of hamsters might selectively induce hepatic CYP1A2 which cannot activate BOP. Consequen tly, the present findings could explain, in part, the anticarcinogenic effect of CS on BOP-induced pancreatic tumors in hamsters. The findin gs further support the idea that CS markedly stimulates the metabolic activation of food-derived carcinogens, which may contribute to the ov erall carcinogenic effects of cigarette smoking.