2-Acetylaminofluorene promotion of liver carcinogenesis by a non-cytotoxic mechanism

Abstract

2-Acetylaminofluorene (AAF), given in the diet at 0.02% for 4 weeks, is an effective promoter of liver carcinogenesis initiated by partial hepatectomy (PH) plus diethylnitrosamine (DEN) in the inbred rat strain Wistar Kyoto. AAF promotes the early (6 week) appearance of phenotypically altered (γ-glutamyltranspeptidase-positive) cells as well as the later appearance of neoplastic nodules (2–4 months) and hepatocarcinomas (4–8 months). Promotion does not seem to involve selective cytotoxkity (selection of AAF-resistant hepatocytes), since neither AAF alone nor DEN+AAF has any inhibitory effect on overall liver growth.