BIOTRANSFORMATION OF SEVERAL STRUCTURALLY RELATED 2B COMPOUNDS TO REACTIVE METABOLITES IN THE SOMATIC W W+ ASSAY OF DROSOPHILA-MELANOGASTER/

Biotransformation of several structurally related 2B compounds to reac tive metabolites was evaluated in the somatic w/w+ assay of Drosophila melanogaster. Chemicals tested were the dichlorinated alkanes dichlor omethane (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 pla stic monomer styrene (SN) and its metabolite styrene 7,8-oxide (SO). T he tester strains used consisted of one wild-type insecticide-suscepti ble (IS) laboratory strain (Leiden-S, ST), and two insecticide-resista nt (IR) strains (Hikone-R, HK, and Haag-R, HG). The latter have high c ytochrome P450-dependent bioactivation capacities. Drosophila larvae h eterozygous for the wild-type report gene w+ were exposed chronically to at least three different exposure doses of each compound. A total o f 53,694 eyes were analyzed. A positive genotoxic activity was obtaine d 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 recombin agenic 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. (C) 1998 Wiley Liss, Inc.