The irreversible binding of benzo[a]pyrene to rat liver macromolecules in vivo and in vitro: Effects of agents that influence benzo[a]pyrene metabolism
The present study was carried out to determine the effects of agents that influence benzo[a]-pyrene(BP)metabolism in vitro on the irreversible binding of BP to rat hepatic macromolecules in vivo. The irreversible binding of [3H]BP was found to be both dose and time dependent after its intraperitoneal administration to male Wistar rats. The SKF 525-A, at doses of 50 and 75 mg/kg, ip, 3 h before BP, decreased the level of binding from control by 31 and 34%, respectively. At 35 mg/kg, SKF 525-A had no effect. Diethyl maleate (0.6 mL/kg, ip) and cysteine (150 mg/kg, ip), 30 and 5 min before BP, respectively, did not alter the binding of BP from control. Oral methadone treatment, previously shown to increase selectively epoxide hydrase activity in male Wistar rats, also failed to alter the amount of BP bound to hepatic macromolecules. 3-Methylcholanthrene (20 mg/kg per day, ip, for 2 days) administered 24 h before BP, decreased the level of binding from control by.30%. Parallel in vitro studies were carried out with the various agents used in vivo.