Mechanisms of cancer chemoprevention in hepatic carcinogenesis : Modulation of focal lesion growth in mice

Studies in our laboratory have concentrated on further understanding the mechanism by which chemicals induce cancer and the means to prevent or retard this process. Recent investigations have revolved around the role of oxidative stress and oxidative damage in the induction of cancer by nongenotoxic carcinogens. Hepatocarcinogenic compounds including selective chlorinated hydrocarbons appeared to induce oxidative stress in the liver. This oxidative stress and oxidative damage in turn may be responsible for the tumor-promoting activity of these compounds. Reduction of oxidative damage by antioxidants, or dietary-restriction, results in an ablation of the induction of selective cell growth by these agents. The oxidative stress induced by nongenotoxic agents may influence cell proliferation and/or apoptosis in the preneoplastic cells. Our studies with nongenotoxic hepatic carcinogens showed a dose-dependent increase in oxidative stress and an increase in hepatic focal lesion growth. Antioxidant dietary supplementation or caloric restriction prevented the lesion growth. This appeared to be through an increase in apoptosis in the hepatic lesions.