COMPENSATORY REGENERATION, MITOGEN-INDUCED LIVER GROWTH, AND MULTISTAGE CHEMICAL CARCINOGENESIS

Liver cell proliferation has often been implicated to play a major rol e during different steps of the carcinogenic process. Most of the expe rimental studies indicating a close association between cell prolifera tion and liver cancer development have made use of a compensatory type of proliferative stimulus. However, liver growth may also be caused b y direct hyperplasia after administration of primary mitogens. Our rec ent studies examined the possible differences between these two types of cell proliferation. Our studies indicate that a) increased expressi on of proto-oncogenes such as c-fos, c-jun, and c-myc is not necessary for entry into the cell cycle during mitogen-induced liver growth; b) mitogen-induced liver growth does not support initiation of chemical hepatocarcinogenesis; c) repeated proliferative stimuli induced by pri mary mitogens do not stimulate the growth of initiated cells to a foca l and/or nodular stage; and d) mitogen-induced liver growth, unlike co mpensatory regeneration, is followed by a particular mode of cell deat h, namely, apoptosis. This type of cell death may be responsible for t he elimination of carcinogen-initiated cells.