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农药混合物诱导的遗传毒性:对人外周血淋巴细胞的体外研究

Genotoxicity induced by pesticide mixtures: in-vitro studies on human peripheral blood lymphocytes.

作者信息

Das P P, Shaik A P, Jamil K

机构信息

Department of Genetics, Bhagwan Mahavir Medical Research Centre, Hyderabad, Andhra Pradesh, India.

出版信息

Toxicol Ind Health. 2007 Sep;23(8):449-58. doi: 10.1177/0748233708089040.

DOI:10.1177/0748233708089040
PMID:18669166
Abstract

To assess the damage caused by pesticides and their mixtures on humans, we designed in-vitro experiments to evaluate their cytotoxicity and genotoxicity. Three equimolar pesticide mixtures were investigated for their capability to affect cultured human peripheral blood lymphocytes. The LC50 values for cytotoxicity, using standard trypan blue dye exclusion and calculated by probit analysis, were 4.18, 5.76, and 7.5 microM for endosulfan, carbofuran, and monocrotophos, respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 0.7, 0.9, and 1.0 microM for monocrotophos + carbofuran, endosulfan + monocrotophos, and endosulfan + carbofuran, respectively, using the method. DNA damage was estimated using chromosomal aberrations (chromatid breaks, fragments, gaps, aneuploidy, and satellite association) and comet assays using 1/10 of the LC50 concentrations. Using a standard alkaline comet assay procedure, high concentrations of individual pesticides (0.5-4.0 microM) caused significant DNA damage as indicated by visible tail lengths. Lower concentrations (0.05-0.5 microM) of their binary mixtures could cause the same effect. The results suggest that analysis of genotoxicity may serve as an important biomarker for occupational and household exposure to pesticides, especially mixtures of pesticides, with different modes of action.

摘要

为评估农药及其混合物对人体造成的损害,我们设计了体外实验来评估它们的细胞毒性和遗传毒性。研究了三种等摩尔浓度的农药混合物对培养的人外周血淋巴细胞的影响能力。使用标准台盼蓝染料排除法并通过概率分析计算得出,硫丹、克百威和久效磷的细胞毒性LC50值分别为4.18、5.76和7.5微摩尔。当以等摩尔浓度混合时,久效磷+克百威、硫丹+久效磷和硫丹+克百威的细胞毒性LC50值分别为0.7、0.9和1.0微摩尔。使用该方法,采用染色体畸变(染色单体断裂、片段、间隙、非整倍体和卫星关联)和彗星试验,以LC50浓度的1/10估计DNA损伤。使用标准碱性彗星试验程序,高浓度的单一农药(0.5 - 4.0微摩尔)会导致明显的DNA损伤,表现为可见的尾巴长度。其二元混合物的较低浓度(0.05 - 0.5微摩尔)也会产生相同的效果。结果表明,遗传毒性分析可能是职业和家庭接触农药,特别是具有不同作用方式的农药混合物的重要生物标志物。

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