Age‐dependent Induction of Preneoplastic Liver Cell Foci by 2‐Acetylammo‐fluorene, Phenobarbital and Acetaminophen in F344 Rats Initially Treated with Diethylnitrosamine

Effects of age on the induction of glutathione S‐transferase placental form (GST‐P)‐positive hepatic foci in rats were examined using a medium‐term liver bioassay system (for carcinogens). F344 male rats aged 6, 26 and 46 weeks were initially given a single intraperitoneal injection of diethylnitro‐samine (DEN, 200 mg/kg) and, beginning 2 weeks later, received 0.02% 2‐acetylaminofluorene (2‐AAF), 0.05% phenobarbital (PB) or 1.3% acetaminophen (AAP) in the diet for 6 weeks. All animals were subjected to two‐thirds hepatectomy 3 weeks after the DEN injection and were killed at week 8. Quantitative analysis of GST‐P‐positive foci revealed significantly (P< 0.001) increased induction over control levels in terms of both numbers and areas for 2‐AAF at all ages (6, 26 and 46 weeks), but especially in the 6‐week‐old case. In the PB‐ and AAP‐treated groups, the respective enhancing and inhibitory influences were most pronounced in the animals aged 6 weeks, and were less marked in older rats. Thus, the response of F344 rats to the modifying effects of chemicals was age‐dependent, the conclusion being drawn that young rats are more susceptible and therefore more appropriate for assessment of carcinogenic, promoting and inhibitory effects of chemicals.