DISTINCT SUBSTRATE-SPECIFICITY OF CYTOCHROME-P450 DEPENDENT MONOOXYGENASE SYSTEM FOR FENVALERATE AND DIAZINON METABOLISM IN PYRETHROID AND ORGANOPHOSPHATE RESISTANT HOUSEFLY STRAINS

The specificity of cytochrome P450 dependent monooxygenases present in housefly microsomes from a susceptible strain, an organophosphate res istant and a Japanese pyrethroid resistant strain was studied using di azinon and fenvalerate as substrates. Both the resistant strains were more active than the susceptible strain in producing O,O-diethyl phosp horothioic acid (DEPTA) as well as the sum of diazoxon and O,O-diethyl phosphoric acid (DEPA) from ethoxy labeled C-14-diazinon. The reactio n was not inhibited by the addition of nonradioactive fenvalerate at a n equivalent concentration. Utilizing TLC, four radioactive metabolite s of phenoxyphenyl-ring labeled C-14-fenvalerate were resolved. They c orresponded to an unknown metabolite A, a mixture of 4-hydroxy-3-pheno xybenzoicacid (4-HO-PBacid) and (+/-)-alpha-cyano-4-hydroxy-3-phenoxyb enzyl (+/-)-alpha-(p-chlorophenyl)isovalerate (4-HO-fenvalerate), 3-ph enoxybenzoic acid (PBacid) and fenvalerate. Compared to the susceptibl e strain, both the resistant strains produced more metabolite A while the pyrethroid resistant strain also produced more PBacid. In contrast , there was little difference in the production of phenoxyphenyl-ring hydroxylated metabolites among the strains. Nonradioactive diazinon in hibited the metaboliSM of C-14-fenvalerate markedly in both the resist ant strains, and the inhibition appeared to be of a non-competitive ty pe. CO binding difference spectra revealed a variation in lambda(max) values; 451.5-452 nm for CSMA, 451-451.5 nm for Yachiyo and 450-450.5 nm for Mashiko strains. These results confirmed the presence in the py rethroid resistant strain of a cytochrome P450 species particularly ac tive in the oxidative ester cleavage of fenvalerate. This P450 species is distinct from the P450s responsible for diazinon metabolism or for the metabolism of fenvalerate to metabolite A; the latter P450s being present in both the resistant strains.