Organochlorine insecticides: impacts on human HepG2 cytochrome P4501A, 2B activities and glutathione levels
Organochlorine insecticides: impacts on human HepG2 cytochrome P4501A, 2B activities and glutathione levels
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DOI：
10.1016/j.tiv.2004.10.002
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发表时间：
2005-03-01
影响因子：
3.2
通讯作者：
Thenappan, A
中科院分区：
文献类型：
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作者：
Dehn, PF;Allen-Mocherie, S;Thenappan, A
研究了有机氯杀虫剂氯丹、o，p '-DDT、狄氏剂、硫丹、酮、甲氧滴滴涕和毒杀芬对人HepG 2细胞色素P450（IA-EROD和2B-PROD）活性和谷胱甘肽（GSH）水平的影响。将细胞在高浓度（1、5或10 mM）下暴露24小时，并在0.01至1 mM的较低浓度下暴露48小时，以评价剂量反应。我们的结果表明，48小时后，除了狄氏剂，所有的P4501 A和2B显着诱导。在所有暴露浓度和时间下，P4502 B反应均较大。观察到GSH水平的混合反应。24 h后，除狄氏剂和MXC外，所有OC均显著耗竭GSH。在48小时，杀虫脒，硫丹和毒杀芬显着增加GSH在低水平和降低GSH在高水平，而开蓬和甲氧滴滴涕在所有浓度下产生的GSH显着下降。这些结果支持OC杀虫剂诱导大鼠CYP 1A，2B的研究结果，CYP 2B反应更重要。当P4502 B活性显著升高时，GSH水平下降，并且在没有显著P450活性的情况下，GSH水平显著增加，这表明GSH水平影响细胞色素P450的催化活性，并且细胞色素P450影响细胞调节GSH的能力。(C)2004爱思唯尔有限公司保留所有权利。
This study examined the effects of the organochlorine (OC) insecticides chlordane, o,p'-DDT, dieldrin, endosulfan, kepone, methoxychlor, and toxaphene on human HepG2 cytochrome P450 (IA-EROD and 2B-PROD) activities and glutathione (GSH) levels. Cells were exposed for 24h at high concentrations (1, 5 or 10mM) and for 48h at lower concentrations ranging from 0.01 to 1 mM to evaluate dose responses. Our results show that after 48h all but dieldrin significantly induced both P4501A and 2B. P4502B responses were greater at all exposure concentrations and times. Mixed responses in GSH levels were observed. All OCs except dieldrin and MXC significantly depleted GSH after 24 h. At 48 h, chlordane, endosulfan and toxaphene significantly increased GSH at low levels and decreased GSH at high levels, while kepone and methoxychlor produced significant declines in GSH at all concentrations. These results support findings of OC insecticides inducing CYP1A, 2B in rats, with CYP2B responses more important. GSH levels declined when P4502B activity was significantly elevated and were significantly increased in the absence of significant P450 activity, suggesting that GSH levels influence the catalytic activity of the cytochrome P450s and the cytochrome P450s influence the cell's ability to regulate GSH. (C) 2004 Elsevier Ltd. All rights reserved.