ANTI-P450(LPR) ANTISERUM INHIBITS THE ACTIVATION OF CHLORPYRIFOS TO CHLORPYRIFOS OXON IN HOUSE-FLY MICROSOMES

Cytochrome P450lpr is a house fly-specific P450 that is developmentally regulated and expressed at higher levels in the insecticide resistant LPR strain compared to susceptible strains. P4SOlpr catalyzes the metabolism of deltamethrin, methoxyresorufin, and benzo[a]pyrene in LPR microsomes. Herein, we report on the role of cytochrome P450lpr in the metabolism of chlorpyrifos and chlorpyrifos oxon. Monooxygenase-mediated oxidative desulfuration of chlorpyrifos in the LPR strain was greater than that in the susceptible S+ strain. Anti-P450lpr antiserum caused complete inhibition of monooxygenase-mediated chlorpyrifos metabolism in S+ and nearly complete inhibition in LPR microsomes. This suggests that P450lpr is the major P450 responsible for chlorpyrifos activation and metabolism in S+ and LPR microsomes. When chlorpyrifos oxon was used as the substrate, the microsomal monooxygenases caused a significant conversion of oxon to water-soluble metabolites in both S+ and LPR microsomes; however, anti-P450lpr antiserum had no significant effect on the amount of chiorpyrifos oxon remaining in S+ and only slightly inhibited this reaction in LPR. This suggests that P450lpr is the major P450 responsible for oxidative desulfuration of chlorpyrifos, but not a major P450 involved in monooxygenase-mediated chlorpyrifos oxon metabolism. The role of P450lpr in the production of specific metabolites is discussed. © 1993 Academic Press.