Differential effects of acetaminophen pretreatment on hepatic aflatoxin B 1-DNA binding, cellular proliferation, and aflatoxin B 1-induced hepatic foci in rats and hamsters

Abstract

Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B 1 (AFB 1)-DNA binding, cellular proliferation, and AFB 1-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600 mg AAP 3 h before AFB 1 i.p. injection showed three-fold more AFB 1-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4–0.6%) 24–96 h after AAP (600 mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72 h after AAP treatment. Dosing of rats with AFB 1 alone at 0.5 or 2.5 mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 μm; pretreatment with AAP (300 or 600 mg) 48 h before 0.5 or 2.5 mg AFB 1 had no effect on the number and focal area of foci. In hamsters, 1 or 2 mg AFB 1 alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600 mg) 48 or 72 h before 1 or 2 mg AFB 1 produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.