HEPATIC ENZYMATIC METABOLISM ALTERATIONS AND OXIDATIVE STRESS DURING THE ONSET OF CARCINOGENESIS - PROTECTIVE ROLE OF ALPHA-TOCOPHEROL

Oxidants play a role in several stages of carcinogenesis. A high antio xidant capacity is expected to protect `initiated' cells from excessiv e oxidant toxicity. The aim of this study was to determine the chemopr eventive effect of alpha-tocopherol (alpha-T) on the hepatocarcinogene sis induced with p-dimethylaminoazobenzene (DAB) in mice. The dietary administration of alpha-T completely reversed the induction of delta-a minolevulinate synthetase and glutathione-S-transferase (the tumoral m arker enzyme). alpha-T greatly enhanced P 450 levels, which were even higher in animals exposed to DAB. Indirect evidence for the involvemen t of oxygen radicals in the DAB model of hepatocarcinogenesis was prov ided by increased levels of thiobarbituric acid reactive species, whic h were detected in animals with severe liver damage and were assessed by histological analysis. alpha-T reduced the degree of hepatic injury , although this vitamin produced only slight changes in the oxidative parameters evaluated. The use of alpha-T as a potential chemopreventiv e agent, particularly during the initiation stage of carcinogenesis pr ovoked by DAB, is worthy of further study. (C) 1998 Rapid Science Ltd.