Biotransformation of several structurally related 2B compounds to reactive metabolites in the somatic w/w+ assay of Drosophila melanogaster.

Abstract

Biotransformation of several structurally related 2B compounds to reactive metabolites was evaluated in the somatic w/w+ assay of Drosophila melanogaster. Chemicals tested were the dichlorinated alkanes dichloromethane (DCM), 1,2-dichloroethane (DCE), and 1,3-dichloropropane (DCP); the thiouracil derivatives 5-methyl, 2-thiouracil (5M2TU), 6-methyl, 2-thiouracil (6M2TU), and 5-propyl, 2-thiouracil (5P2TU); and the plastic monomer styrene (STY) and its metabolite styrene 7,8-oxide (SO). The tester strains used consisted of one wild-type insecticide-susceptible (IS) laboratory strain (Leiden-S, ST), and two insecticide-resistant (IR) strains (Hikone-R, HK, and Haag-R, HG). The latter have high cytochrome P450-dependent bioactivation capacities. Drosophila larvae heterozygous for the wild-type report gene w+ were exposed chronically to at least three different exposure doses of each compound. A total of 53,694 eyes were analyzed. A positive genotoxic activity was obtained for DCM and for 6M2TU at all exposure doses and genotypes analyzed, and for SO in the IR strains HK-R and HG-R. An overall weakly recombinagenic response was shown by DCE and 5M2TU. The chemicals DCP, 5P2TU, and STY proved to be overall negative in IR as well as in IS strains, and SO was negative in the standard stock. Biotransformation mediated by cytochrome P450 monoxigenases to reactive metabolites is discussed.