Simultaneous induction of liver cirrhosis and hepatocellular carcinomas in F-344 rats: establishment of a short hepatocarcinogenesis model.
The relationship between liver cirrhosis and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F-344 rats was studied. Hepatic cirrhosis was produced by combined administration of CCl4 (0.5 ml/kg b.w. by gavage, three times a week) and phenobarbital (PB) (0.05% in drinking water, continuously for 6 weeks), while the carcinogenic nitrosamine compound was given either preceding or following CCl4 + PB treatment at a single dose of 200 mg/kg b.w., ip. Liver lesions were evaluated histologically at the end of the 4th month. The established cirrhosis completely prevented the formation of hepatocellular carcinomas (HCCs), however, CCl4 + PB posttreatment resulted in a strong enhancing effect on DEN-hepatocarcinogenesis: 16 weeks after initiation severe cirrhosis and HCCs occurred simultaneously in more than 90% of the animals. Although the explanation of this highly accelerated carcinoma formation is not known at present, the authors hypothesize that the modulation of the drug-metabolizing enzyme system might play a central role in this profoundly altered host response.
Zalatnai
A
A
1st Institute of Pathology and Experimental Cancer Research Semmelweis Medical University, Budapest, Hungary.
Lapis
K
K
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity; D006498:Hepatectomy; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D002273:Carcinogens; D004052:Diethylnitrosamine; D002251:Carbon Tetrachloride; D010634:Phenobarbital