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溶剂暴露人群的基因多态性及其与三氯乙烯对淋巴细胞体外效应的相关性研究。

Study of genetic polymorphism in solvent exposed population and its correlation to in vitro effect of trichloroethylene on lymphocytes.

作者信息

Kumar Munish, Tewari Shikha, Sharma Priti, Verma Vipin Kumar, Chauhan L K S, Agarwal Sudhir Kumar, Dwivedi U N, Goel Sudhir Kumar

机构信息

Petroleum Toxicology Division, Indian Institute of Toxicology Research, Lucknow-226 001, India.

出版信息

J Environ Biol. 2009 Sep;30(5):685-91.

Abstract

Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity still not much is known about its genotoxic potential on humans in relation to genetic polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs) are important in cellular detoxification of TCE. Variations in gene sequences result in population specific regional genetic variations (polymorphism). Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220 normal and 97 solvent-exposed individuals from northern part of India using real time PCR, PCR and restriction digestion techniques. The parameters examined to study genotoxicity were chromosomal aberration (CA) and cytokinesis block micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or (ile/val) or(val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9% respectively. It was further observed that the frequencies of above genes were found to be similar in solvent exposed groups. The distribution frequencies of GST genes, when compared with other reports from various regions of India show variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant genotoxic effect. TCE maybe toxic due to its metabolite.

摘要

三氯乙烯(TCE)是一种污染环境的主要工业污染物。接触TCE可能导致肝肾功能毒性以及癌症进展。尽管对其毒性进行了广泛研究,但关于其与基因多态性相关的对人类的遗传毒性潜力仍知之甚少。细胞色素P450(CYP P - 450)和谷胱甘肽 - S - 转移酶(GSTs)在TCE的细胞解毒过程中起重要作用。基因序列的变异导致特定人群的区域遗传变异(多态性)。使用实时PCR、PCR和限制性消化技术,对印度北部220名正常人和97名溶剂暴露个体进行了CYP1A1、GSTM1、GSTT1和GSTP1多态性的基因分型。用于研究遗传毒性的检测参数是体外淋巴细胞培养中的染色体畸变(CA)和胞质分裂阻滞微核试验(CBMN)。在正常受试者中,观察到的GSTM1(缺失)和GSTT1(缺失)的平均频率分别为41%、22%和12.7%,而CYP1A1/GSTP1具有(ile/ile)或(ile/val)或(val/val)的频率分别为76.2/52、21.4/42.1和2.4/5.9%。进一步观察发现,上述基因的频率在溶剂暴露组中相似。与印度不同地区的其他报告相比,GST基因的分布频率存在差异。体外TCE暴露(2、4和或6 mM)未显示任何显著的遗传毒性作用。TCE可能因其代谢产物而具有毒性。

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