Decreased Sensitivity to Phalloidin of Normal‐looking Rat Hepatocytes after Short‐term 2‐Acetylaminofluorene Feeding

Male F344/DuCrj rats were fed a diet containing 0.02% 2‐acetylaminofluorene (2‐AAF) for 1 or 3 weeks, and then fed a basal diet for 2 days, 2 weeks, 8 weeks, 22 weeks or 36 weeks. Hepatocytes were isolated from the liver by collagenase perfusion, and their sensitivity to phalloidin, in terms of the formation of multiple cytoplasmic blebs, was examined. The sensitivity of gamma‐glutamyltransferase (GGT)‐negative hepatocytes decreased on the 22nd and 36th weeks after withdrawal of 2‐AAF feeding, and that of GGT‐positive cells decreased on the 36th week. Induction of a small number of foci positive for the placental form of glutathione S‐transferase (GSTP) was observed in the liver of all rats on the 8th, 22nd and 36th weeks after the withdrawal of the carcinogen. However, the total area of the foci was estimated to account for less than 0.2% of liver tissues even on the 36th week. Therefore, the decrease in phalloidin sensitivity of hepatocytes, particularly of GGT‐negative hepatocytes, on the 22nd and 36th weeks after 2‐AAF withdrawal is suggested to be a result of a decrease in the sensitivity of otherwise normal‐looking hepatocytes, which may be precursors of the cells forming the preneoplastic foci.