Cell proliferation and promotion of rat liver carcinogenesis: different effect of hepatic regeneration and mitogen induced hyperplasia on the development of enzyme-altered foci

A series of experiments was performed to investigate the effectof different types of cell proliferation on the developmentof enzyme-altered preneoplastic hepatic foci in male Wistarrats. Animals were given a single dose of diethylnitrosamine(100 mg/kg body weight). After a 2-week recovery period livercell proliferation was repeatedly induced by four or eight necrogenicdoses of carbon tetrachloride (compensatory cell proliferation),or by four or eight treatments with three different liver mitogens,namely lead nitrate, ethylene dibromide and nafenopin (directhyperplasia). The carcinogen altered hepatocytes were monitoredas --glutamyltransferase positive or adenosine triphosphatasenegative foci. The results indicate that compensatory cell proliferationinduced by both four and eight carbon tetrachloride treatmentsenhanced the growth of diethylnitrosamine-initlated hepatocytesto enzyme- altered foci. On the contrary, repeated waves ofcell prolifera tion induced by liver mitogens did not resultin any significant number of enzyme-altered foci.