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Effect of the Organophosphate Insecticide Parathion and Its Active Metabolite Paraoxon on the Metabolism of Benzo(a)pyrene in the Rat¹

Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Pretreatment of rats with the organophosphate insecticide parathion (0.7 mg/kg) and its active metabolite paraoxon (0.3 mg/kg) i.p. once daily for 5 days before the i.v. administration of carbon-labeled benzo(a)pyrene (BP-¹⁴C) on the 6th day decreased the rate of biliary excretion of radioactive metabolites derived from BP-¹⁴C. Decreased bile flow did not account for this finding since the rate of bile flow was not affected by treatment with these organophosphates. Parathion and paraoxon treatment increased the amount of unchanged BP-¹⁴C and decreased the amount of BP-¹⁴C metabolites in liver and small intestine but not in lung, when measured 95 min after i.v. administration BP-¹⁴C. In vitro studies of the hydroxylation of benzo(a)-pyrene (BP) showed a decreased activity of BP hydroxylase in liver, small intestine, and lung of rats previously treated with these organophosphates. BP hydroxylase activity was also inhibited when parathion or paraoxon was added directly to the incubation medium containing homogenates of liver, small intestine, and lung. These findings indicate that both parathion and paraoxon inhibit the in vivo and in vitro metabolism of BP.

¹ This investigation was supported by USPHS General Research Support Grant RR-5415 and USPHS Grant ES00507. A preliminary report of this study was given previously (20).

² To whom requests for reprints should be sent, at Department of Pharmacology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pa. 19107.

Received 11/ 2/73. Accepted 1/25/74.