chapter  3
30 Pages

Chemical-Induced Hepatocarcinogenesis

ByJames E. Klaunig, Kyle L. Kolaja

The study of chemical-induced hepatocarcinogenesis has provided strong insight into the tumor formation process. A variety of chemicals and agents can increase the incidence, multiplicity, or time of onset of hepatic cancer. These compounds either damage DNA (genotoxic) or produce cancer through epigenetic (nongenotoxic) mechanisms. Compounds that produce hepatic cancer through these epigenetic mechanisms exert a variety of effects including changes in methylation, oxidative stress, gene expression, protein kinase C activity, gap junctional intercellular communication, mixed function oxidase activity, and growth factor expression. The most important effect nongenotoxic hepatocarcinogens have on hepatocytes is the induction of initiated cell growth through increased cell proliferation or decreased cell death (apoptosis). This chapter examines several aspects of chemical-induced hepatocarcinogenesis including the multistage model ofhepatocarcinogenesis, quantification oflesion growth, the impact that carcinogens have on cell proliferation and apoptosis, and the possible mechanisms that are involved in carcinogen-induced imbalances in growth parameters that lead to hepatic cancer.