ACTIVE CELL-DEATH - ROLE IN HEPATOCARCINOGENESIS AND SUBTYPES

Active cell death, the genetically programmed self-destruction of a ce ll, is now recognized to be a widespread phenomenon in biology that co unterbalances mitosis to preserve tissue homeostasis. It is subject to the control of the growth regulatory networks in tissues. Close exami nation of the morphology of dying cells in liver and other tissues sug gests that there are a number of morphological types of active cell de ath, ranging from forms dominated by nuclear changes and without signs of autophagy (''classical'' apoptosis), e.g., in thymocytes and the l iver, to those dominated by autophagic degradation of cytoplasm, e.g., in the mammary gland. The induction of gene expression in these diver se types of cell death is anticipated to be different. Here we review the data regarding the regulation of apoptosis in the liver by liver t umor promoter, transforming growth factor P-l and related peptides as well as nutrition. In the course of hepatocarcinogenesis, initiated ce lls as well as preneoplastic and neoplastic cell populations showed en hanced cell replication, but also enhanced apoptosis. Tumor promoter s hift the balance between birth and death by increasing the rate of cel l replication and by decreasing the rate of apoptosis. Thereby, liver tumor formation is accelerated. Food restriction exhibits the opposite effect and consequently, provides protection from carcinogenesis.