7 - Apoptosis and hepatocarcinogenesis

Abstract

This chapter discusses the relationship between apoptosis and hepatocarcinogenesis. In normal liver both cell replication and cell death by apoptosis are involved in the homeostasis of cell number. Both processes occur in a coordinated, coupled manner. Hepatic growth stimuli tend to increase cell replication and decrease cell death, whereas during the regression of liver size cell replication declines and apoptosis goes up. In the preneoplastic and neoplastic liver, the rates of cell replication and of apoptosis are both higher than in the normal tissue. However, the coordination and coupling between both events as noted in normal liver tissue is still maintained. As a result, preneoplastic and neoplastic tissue may still exhibit a partial balance between cell replication and cell elimination. Preneoplastic liver cells seem to exhibit an intrinsic defect in growth control, rendering them more susceptible to certain signals stimulating growth or regression of liver tissue. Treatment with a tumor promoter will shift the balance favoring cell proliferation; the preferential response of foci results in the accumulation of preneoplastic cells and, thereby, in the acceleration of tumor development. Conversely, promoter withdrawal or food restriction favors active cell death; this may result in the preferential elimination of initiated and preneoplastic cells and thereby, in the extinction of initiated clones and in the regression of preneoplastic lesions and even of tumors. Nongenotoxic carcinogens that are liver tumor promoters are mitogens for normal as well as for preneoplastic and neoplastic liver cells. In addition, these agents act as survival factors for preneoplastic cells. The anti-initiating, antipromoting, and anticarcinogenic effects of actively induced cell death are of interest for the design of new chemopreventive and therapeutic strategies against cancer.