LIPID-PEROXIDATION AND ETHANOL-RELATED TUMOR PROMOTION IN FISCHER-344RATS TREATED WITH TOBACCO-SPECIFIC NITROSAMINES

Male Fischer-344 rats were treated, by gavage, with a total dose of 40 mmol/kg of N'-nitrosonornicotine (NNN) or 20 mmol/kg of 4-(methylnitr osamino)-1-(3-pyridyl)-1-butanone (NNK), three times a week for 4 week s. One week afterwards the rats were fed an isocaloric liquid diet con taining 7% (v/v) ethanol and continued on this diet until killed. Cumu lative ethane exhaled by a rat by 180 min was measured at 54 weeks of the start of the study and was found to increase significantly (P < 0. 001) with either NNN or NNK treatment but more so when followed by eth anol consumption. Other indices of lipid peroxidation, cholesterol and phospholipids were measured in the lipid extracts from the liver, eso phagus and lungs at 55 weeks. Ethanol consumption increased the amount of cholesterol and phospholipids per g of tissue in naive or NNN- and NNK-treated rats. All peroxidative indices measured, i.e. malondialde hyde (MDA), diene- and triene-conjugates and lipid fluorescence, were significantly increased in the liver, the main metabolic and peroxidat ive site, with ethanol consumption in rats whether they were treated w ith NNN or NNK or remained untreated. Overall, the indices of lipid pe roxidation also showed an increase in other tissues, but the results d iffered with different indices. the differences in indices may be due to differences in lipid peroxidation products measured or to differenc es in their rates of production and degradation or conversion to other products. However, the largest increases in indices were seen with et hanol consumption by either NNN- or NNK-treated rats. Incidence of tum ors in the tissues was also assessed and showed about a two-fold incre ase with ethanol consumption in the tumors of esophagus, oral cavity, lungs and liver induced by either NNN or NNK. Ethanol also caused an i ncreased in the mean frequency and mean size of the tumors induced. Th e results suggest that ethanol-related promotion of NNN- and NNK-induc ed tumors may result from increased lipid peroxidation in the target t issue.