Reactive oxygen species (ROS) are implicated in both initiation and promotion in multistage carcinogenesis. Therefore antioxidant systems, which act against ROS may play important roles in cancer development. In this dissertation, rat hepatocarcinogenesis was selected as a model of carcinogenesis. Phenobarbital (PB) and fumonisins were used as model cancer promoters, and soybean isoflavone extract was investigated as a model antioxidant anticarcinogen in PB-promoted rat liver. The expression of two S-thiolatable cytosolic enzymes, the [pi] class of rat glutathione S-transferase (rGST P1-1) and carbonic anhydrase III (CA III) was investigated in rat hepatocarcinogenesis. Understanding the relationship of these enzymes to carcinogenesis is important, given the proposed role of protein S-thiolation/dethiolation as an antioxidant mechanism;After initiation by diethylnitrosamine (DEN), and during promotion of male rat liver carcinogenesis stimulated by fumonisin treatment, rGST P1-1 level was increased 10 fold, whereas CA III level was suppressed by 43% in hepatic cytosolic fraction. Therefore CA III as well as rGST P1-1 may serve as a marker of fumonisin-promoted hepatocarcinogenesis;In a model system for hepatocarcinogenesis initiated by DEN and promoted by PB, soybean isoflavone extract (920 or 1840 [mu]mol/kg diet) normalized total hepatic glutathione peroxidase activity (GPX) which was decreased after 3 months of feeding PB. Both doses of isoflavone extract suppressed promotion after 3 mos of PB feeding, assessed by rGST P1-1 as a biomarker of altered hepatic foci, suggesting that the anticarcinogenic action of isoflavones may be related to isoflavone effect on total GPX;The S-thiolation of rGST P1-1 was directly identified by isoelectric focusing technique. In addition, a dimer was formed between subunits of rGST P1-1 during diamide treatment. This suggests that this [pi] class enzyme is under control at the thiol/disulfide level during cancer development;The overexpression of rGST P1-1 during rat hepatic carcinogenesis, its selenium independent glutathione peroxidase activity and its ability to undergo S-thiolation/dethiolation suggest that this [pi] class enzyme is a candidate to function as an antioxidant system protecting preneoplastic and neoplastic cells during their growth.