The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon
The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon
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DOI：
10.1016/s0300-483x(02)00592-9
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发表时间：
2003-03-14
期刊：
影响因子：
4.5
通讯作者：
McLean, WG
中科院分区：
文献类型：
--
作者：
Axelrad, JC;Howard, CV;McLean, WG
关于长期接触低剂量有机磷农药可能导致神经毒性的推测尚未得到实验证据的支持。这项工作的目的是使用慢性OP暴露的细胞培养模型，以确定这种暴露是否可以改变神经细胞对随后急性暴露于OP或其他化合物的敏感性。NB2a神经母细胞瘤细胞在25 μ M二嗪农存在下生长8周。然后将OP撤回，并在各种其他杀虫剂或除草剂（包括OP和含OP的制剂）存在下诱导细胞分化。通过光学显微镜和定量图像分析测量所得的神经突样结构的生长，并计算每种OP或制剂的IC 50。将二嗪农预暴露细胞中的IC 50值与未预暴露于二嗪农的细胞中的等效值进行比较。在用二嗪农预处理后，通过二嗪农、除虫菊、草甘膦或草甘膦的商业制剂的急性应用抑制神经突生长的IC 50降低了20%至90%。相比之下，甲基嘧啶磷的IC 50不受影响，而甲基嘧啶磷或毒死蜱的IC 50增加了1.5至3倍。用毒死蜱或用第二种含有草甘膦的制剂处理细胞导致二嗪磷预暴露细胞中异常神经突样结构的形成。这些数据支持这样一种观点，即长期接触有机磷可能会降低某些环境剂的毒性阈值，但绝不是所有环境剂的毒性阈值。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 muM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC50 for each OP or formulation was calculated. The IC50 values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC50 for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC50 for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.