ROLE OF ACTIVE CELL-DEATH (APOPTOSIS) IN MULTISTAGE CARCINOGENESIS

Active cell death is a genetically encoded self-destruction of a cell. There occur morphologically different types of active cell death, e.g . apoptosis in the liver or autophagic cell death in human mammary car cinoma cells after tamoxifen treatment. (Pre)neoplastic lesions in rat liver exhibit enhanced rates of apoptosis, which tend to increase wit h increasing malignancy. Tumor promoters and non-genotoxic carcinogens inhibit active cell death, thereby increasing the accumulation of (pr e)neoplastic cells and accelerating the development of cancer. On the other hand promoter withdrawal, fasting or application of negative gro wth signals such as transforming growth factor beta 1 (TGF beta 1) enh ance apoptosis and can lead to selective regression of preneoplastic l esions or tumors.