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) hepatocarcinogenesis 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.