Inhibitory and promoting effects of carbon tetrachloride-induced liver cirrhosis on the diethylnitrosamine hepatocarcinogenesis in rats.

The modifying effect of the experimentally induced liver cirrhosis on the diethylnitrosamine (DENA)-hepatocarcino-genesis was investigated in male Fischer 344 rats. Cirrhosis was produced by either repeated intragastric doses of CCl4 for 3 months or by simultaneous administration of CCl4 and phenobarbital (PB) in drinking water for 6 weeks. The hepatocarcinogenic regimen consisted of multiple ip. administrations of DENA (10 mg/kg b.w. per dose, up to a total dose of 200 mg/kg b.w.). All the animals were killed 8 months after starting the experiment. The chronic CCl4-post-treatment exerted a strong promoting effect, while the established cirrhosis completely prevented the formation of hepatocellular carcinomas.