Abstract
Organophosphate (OP) pesticides are biotransformed into metabolites such as dialkylphosphates (DAPs). We have evaluated the genotoxicity of malathion and its metabolite dimethylthiophosphate (DMTP) in the human hepatic cell lines HepG2 and WRL-68 and in peripheral blood mononuclear cells (PBMC). In the Cytokinesis-Block Micronucleus assay (CBMN), malathion and DMTP increased the frequencies of micronuclei (MN) and nucleoplasmic bridges (NPB). Malathion was primarily clastogenic whereas DMTP was aneuploidogenic. When HepG2 or WRL-68 cells were treated with DMTP in the presence of sulconazole, a non-specific cytochrome P450 inhibitor, MN frequency was reduced, indicating that DMTP genotoxicity requires P450-cataliyzed metabolism.
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