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

Studies in our laboratory have concentrated on further understanding the me chanism by which chemicals induce cancer and the means to prevent or retard this process. Recent investigations have revolved around the role of oxida tive 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 oxidati ve stress and oxidative damage in turn may be responsible for the tumor-pro moting activity of these compounds. Reduction of oxidative damage by antiox idants, or dietary-restriction, results in an ablation of the induction of selective cell growth by these agents. The oxidative stress induced by nong enotoxic agents may influence cell proliferation and/or apoptosis in the pr eneoplastic cells. Our studies with nongenotoxic hepatic carcinogens showed a dose-dependent increase in oxidative stress and an increase in hepatic f ocal lesion growth. Antioxidant dietary supplementation or caloric restrict ion prevented the lesion growth. This appeared to be through an increase in apoptosis in the hepatic lesions.