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甲基对硫磷、毒死蜱和二嗪农及其氧代代谢物对人类精子的精子染色质改变和DNA损伤

Sperm chromatin alteration and DNA damage by methyl-parathion, chlorpyrifos and diazinon and their oxon metabolites in human spermatozoa.

作者信息

Salazar-Arredondo Elsa, de Jesús Solís-Heredia María, Rojas-García Elizabeth, Hernández-Ochoa Isabel, Quintanilla-Vega Betzabet

机构信息

Sección Externa de Toxicología, CINVESTAV-IPN, Mexico City 07360, Mexico.

出版信息

Reprod Toxicol. 2008 Aug;25(4):455-60. doi: 10.1016/j.reprotox.2008.05.055. Epub 2008 May 21.

DOI:10.1016/j.reprotox.2008.05.055
PMID:18595656
Abstract

Extensive use of organophosphorous pesticides (OP) by young men represents a public health problem. Toxicity of OP mainly results in neurotoxicity due to their oxygen analogues (oxons), formed during the OP oxidative activation. OP alter semen quality and sperm chromatin and DNA at different stages of spermatogenesis. Oxons are more toxic than the parent compounds; however, their toxicity to spermatogenic cells has not been reported. We evaluated sperm DNA damage by several OP compounds and their oxons in human spermatozoa from healthy volunteers incubated with 50-750 microM of methyl-parathion (MePA), methyl-paraoxon (MePO), chlorpyrifos (CPF), chlorpyrifos-oxon (CPO), diazinon (DZN) or diazoxon (DZO). All concentrations were not cytotoxic (evaluated by eosin-Y exclusion), except 750 microM MePO. Oxons were 15% to 10 times more toxic to sperm DNA (evaluated by the SCSA parameter, %DFI) than their corresponding parent compounds, at the following order: MePO>CPO=MePA>CPF>DZO>DZN, suggesting that oxon metabolites participate in OP sperm genotoxicity.

摘要

年轻男性广泛使用有机磷农药(OP)是一个公共卫生问题。OP的毒性主要源于其在氧化活化过程中形成的氧类似物(氧磷)导致的神经毒性。OP在精子发生的不同阶段会改变精液质量以及精子染色质和DNA。氧磷比母体化合物毒性更大;然而,尚未有关于其对生精细胞毒性的报道。我们用50 - 750微摩尔的甲基对硫磷(MePA)、甲基对氧磷(MePO)、毒死蜱(CPF)、毒死蜱氧磷(CPO)、二嗪农(DZN)或二嗪磷(DZO)处理健康志愿者的人类精子,评估了几种OP化合物及其氧磷对精子DNA的损伤。除750微摩尔的MePO外,所有浓度均无细胞毒性(通过伊红-Y排斥法评估)。氧磷对精子DNA的毒性(通过精子染色质结构分析参数%DFI评估)比其相应的母体化合物高15%至10倍,顺序如下:MePO>CPO = MePA>CPF>DZO>DZN,这表明氧磷代谢物参与了OP对精子的遗传毒性。

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