Cytochrome b(5) is essential for cytochrome P450 6D1-mediated cypermethrin resistance in LPR house flies

Cytochrome P450 monooxygenase-mediated detoxification is a very important mechanism of resistance to insecticides. In the LPR strain of house fly, the major mechanism of resistance to pyrethroids is monooxygenase-mediated metabolism due to the overexpression of cytochrome P450 6D1 (CYP6D1). Although the role of CYP6D1 in pyrethroid resistance has been demonstrated, there is no information as to whether cytochrome b(5) is involved in this reaction and what the major CYP6D1-specific metabolite is. Using a cytochrome b(5) antiserum we demonstrate that cytochrome b(5) is required for the elevated level of CYP6D1-mediated cypermethrin metabolism observed in microsomes from the resistant LPR strain compared to a suspectible strain. Therefore, cytochrome b(5) is directly involved in this monooxygenase-mediated resistance. NADH has no significant effect on this metabolism, suggesting that in vitro the second electron source for CYP5D1 is NADPH when cypermethrin is in substrate. Using GC-MS, the primary CYP6D1 specific metabolite formed in vitro was identified as 4'-OH cypermethrin. (C) 1996 Academic Press, Inc.