...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Environmental and molecular mutagenesis. >Effects of model organophosphorous pesticides on DNA damage and proliferation of HepG2 cells.
【24h】

Effects of model organophosphorous pesticides on DNA damage and proliferation of HepG2 cells.

机译：模型有机磷农药对HepG2细胞DNA损伤和增殖的影响。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Organophosphorous compounds (OPs) are commonly used pesticides. The primary mechanism of OP toxicity is the inhibition of acetylcholine esterase in the nervous system leading to a variety of acute and chronic effects. Recent studies have revealed several other targets of OPs that disturb noncholinergic biological systems. We investigated whether low concentrations of model OPs-methyl parathion (PT), methyl paraoxon (PO), and dimefox (DF)-induce DNA damage and/or affect cell proliferation in human hepatoma HepG2 cells. Genotoxicity of OPs was evaluated using the comet assay. The effect on cell proliferation was tested using the MTT assay and proliferation marker Ki-67 immunocytochemistry. The effects of OPs on mRNA expression of the DNA damage responsivegenes p53, p21, GADD45alpha, and MDM2 were determined using qRT-PCR. PT induced DNA damage at lower concentrations (1 microg/mL) than PO (100 microg/mL), whereas DF did not induce DNA damage. PT and PO caused a reduction of cell proliferation at their highest concentrations (100 microg/mL), while DF increased cell proliferation at all concentrations used (0.01-100 microg/mL). PT and PO upregulated expression of DNA damage responsive genes, while DF upregulated expression of p53, downregulated expression of p21, and had no effect on the expression of MDM2 and GADD45alpha. We conclude that PT and PO are genotoxic, while DF shows mitogenic activity. An important finding of this study is that PT had higher genotoxic potential than PO, which warrants for further investigations to correctly evaluate the hazards of exposure to these chemicals.
机译：有机磷化合物（OPs）是常用的农药。 OP毒性的主要机制是抑制神经系统中的乙酰胆碱酯酶，从而导致各种急性和慢性作用。最近的研究表明，OP的其他几个目标会干扰非胆碱能生物系统。我们调查了低浓度的模型OPs-甲基对硫磷（PT），甲基对氧磷（PO）和二甲氟醚（DF）是否会导致DNA损伤和/或影响人肝癌HepG2细胞的细胞增殖。使用彗星试验评估OP的遗传毒性。使用MTT测定法和增殖标记物Ki-67免疫细胞化学测试了对细胞增殖的影响。使用qRT-PCR确定OP对DNA损伤反应基因p53，p21，GADD45alpha和MDM2 mRNA表达的影响。 PT以低于PO（100 microg / mL）的浓度（1 microg / mL）诱导DNA损伤，而DF不诱导DNA损伤。 PT和PO在最高浓度（100 microg / mL）下导致细胞增殖减少，而DF在所有使用浓度（0.01-100 microg / mL）下均增加细胞增殖。 PT和PO上调DNA损伤反应基因的表达，而DF上调p53的表达，下调p21的表达，并且对MDM2和GADD45alpha的表达没有影响。我们得出结论，PT和PO具有遗传毒性，而DF显示有丝分裂活性。这项研究的重要发现是PT具有比PO高的遗传毒性潜力，这有待进一步研究以正确评估接触这些化学物质的危害。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号