Simultaneous induction of liver cirrhosis and hepatocellular carcinomas in F-344 rats: establishment of a short hepatocarcinogenesis model

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalExperimental and Toxicologic Pathology
Volume46
Issue number3
DOIs
Publication statusPublished - Jan 1 1994

Keywords

  • Animal models, hepatocarcinogenesis
  • CCl
  • Diethylnitrosamine
  • Hepatocarcinogenesis
  • liver cirrhosis, experimentally induced

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Cell Biology

Fingerprint Dive into the research topics of 'Simultaneous induction of liver cirrhosis and hepatocellular carcinomas in F-344 rats: establishment of a short hepatocarcinogenesis model'. Together they form a unique fingerprint.

  • Cite this