Abstract
The specificity of cytochrome P450 dependent monooxygenases present in housefly microsomes from a susceptible strain, an organophosphate resistant and a Japanese pyrethroid resistant strain was studied using diazinon and fenvalerate as substrates. Both the resistant strains were more active than the susceptible strain in producing O, O-diethyl phosphorothioic acid (DEPTA) as well as the sum of diazoxon and O, O-diethyl phosphoric acid (DEPA) from ethoxy labeled 14C-diazinon. The reaction was not inhibited by the addition of nonradioactive fenvalerate at an equivalent concentration. Utilizing TLC, four radioactive metabolites of phenoxyphenyl-ring labeled 14C-fenvalerate were resolved. They corresponded to an unknown metabolite A, a mixture of 4-hydroxy-3-phenoxybenzoicacid (4-HO-PBacid) and (±)-α-cyano-4-hydroxy-3-phenoxybenzyl (±)-α-(p-chlorophenyl) isovalerate (4-HO-fenvalerate), 3-phenoxybenzoic acid (PBacid) and fenvalerate. Compared to the susceptible 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 inhibited the metabolism of 14C-fenvalerate markedly in both the resistant strains, and the inhibition appeared to be of a non-competitive type. CO binding difference spectra revealed a variation in λmax values; 451.5-452nm for CSMA, 451-451.5nm for Yachiyo and 450-450.5nm for Mashiko strains. These results confirmed the presence in the pyrethroid resistant strain of a cytochrome P450 species particularly active 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.
