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.

有机磷 (OP) 农药被生物转化为代谢物，例如磷酸二烷基酯 (DAP)。我们已经评估了马拉硫磷及其代谢物二甲基硫代磷酸酯 (DMTP) 在人肝细胞系 HepG2 和 WRL-68 以及外周血单核细胞 (PBMC) 中的遗传毒性。在细胞分裂阻滞微核试验 (CBMN) 中，马拉硫磷和 DMTP 增加了微核 (MN) 和核质桥 (NPB) 的频率。马拉硫磷主要是致裂的，而 DMTP 是非整倍体的。当 HepG2 或 WRL-68 细胞在磺康唑（一种非特异性细胞色素 P450 抑制剂）存在下用 DMTP 处理时，MN 频率降低，表明 DMTP 基因毒性需要 P450 催化代谢。