CYTOCHROME B(5) IS ESSENTIAL FOR CYTOCHROME-P450 6D1-MEDIATED CYPERMETHRIN RESISTANCE IN LPR HOUSE-FLIES

Cytochrome P450 monooxygenase-mediated detoxification is a very import ant mechanism of resistance to insecticides. In the LPR strain of hous e fly, the major mechanism of resistance to pyrethroids is monooxygena se-mediated metabolism due to the overexpression of cytochrome P450 6D 1 (CYP6D1). Although the role of CYP6D1 in pyrethroid resistance has b een demonstrated, there is no information as to whether cytochrome b(5 ) is involved in this reaction and what the major CYP6D1-specific meta bolite is. Using a cytochrome b(5) antiserum we demonstrate that cytoc hrome b(5) is required for the elevated level of CYP6D1-mediated cyper methrin metabolism observed in microsomes from the resistant LPR strai n compared to a suspectible strain. Therefore, cytochrome b(5) is dire ctly involved in this monooxygenase-mediated resistance. NADH has no s ignificant effect on this metabolism, suggesting that in vitro the sec ond electron source for CYP5D1 is NADPH when cypermethrin is in substr ate. Using GC-MS, the primary CYP6D1 specific metabolite formed in vit ro was identified as 4'-OH cypermethrin. (C) 1996 Academic Press, Inc.