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基于诱导的 GADD153-GFP 报告基因表达的杀虫剂硫丹的遗传毒性评价。

Genotoxic evaluation of the insecticide endosulfan based on the induced GADD153-GFP reporter gene expression.

机构信息

College of Life Sciences, Graduate University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Environ Monit Assess. 2011 May;176(1-4):251-8. doi: 10.1007/s10661-010-1580-7. Epub 2010 Jul 14.

Abstract

Endosulfan is one of the few organochlorine insecticides still in use in China for protecting crops from a variety of insects. Endosulfan is toxic in fishes and rodents in the in vivo assays, but its genotoxicity in mammalian cells has not been well tested. In this work, a genotoxic testing system has been developed based on the induction of a HepG2/GADD153-GFP reporter gene expression in response to the DNA-damaging agents. Methyl methanesulfonate, a known carcinogenic and genotoxic agent, was used to test the effects of damage dose and post-treatment incubation time on GADD153-GFP expression. Subsequently, the system was applied to the genotoxicity evaluation of endosulfan. Endosulfan was able to cause the increase of GADD153-GFP expression at a sublethal dose (0.02-20 mg/L). In particular, it induced a maximum green fluorescent protein expression at the tested concentration of 0.2 mg/L, with 4.07-fold inflorescence relative to untreated cells. The results suggest that endosulfan has the potential genotoxicity for HepG2 cell line by inducing DNA damage. The study also confirms that the induced GADD153-GFP expression system is an appropriate and sensitive method for the assessment of genotoxicity from a broad range of pesticides with the DNA-damaging potential.

摘要

硫丹是中国目前仍在使用的少数几种有机氯杀虫剂之一,用于防治多种作物害虫。在体内试验中,硫丹对鱼类和啮齿类动物具有毒性,但尚未对其在哺乳动物细胞中的遗传毒性进行充分测试。本研究基于 DNA 损伤剂诱导 HepG2/GADD153-GFP 报告基因表达,建立了一种遗传毒性测试系统。甲磺酸甲酯是一种已知的致癌和遗传毒性物质,用于测试损伤剂量和处理后孵育时间对 GADD153-GFP 表达的影响。随后,将该系统应用于硫丹的遗传毒性评价。硫丹能够在亚致死剂量(0.02-20 mg/L)下引起 GADD153-GFP 表达增加。特别是,在 0.2 mg/L 的测试浓度下,它诱导了最大的绿色荧光蛋白表达,与未处理的细胞相比,增加了 4.07 倍。结果表明,硫丹通过诱导 DNA 损伤对 HepG2 细胞系具有潜在的遗传毒性。该研究还证实,诱导的 GADD153-GFP 表达系统是一种适当且敏感的方法,可用于评估具有 DNA 损伤潜力的广泛的农药的遗传毒性。

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