细胞色素P450依赖单加氧酶以及GSTT1和GSTM1基因多态性变体在长期接触汞的个体脑损伤形成中的作用。

Role of cytochrome P450-dependent monooxygenases and polymorphic variants of GSTT1 and GSTM1 genes in the formation of brain lesions in individuals chronically exposed to mercury.

作者信息

Chernyak Yu I, Itskovich V B, D'yakovich O A, Kolesnikov S I

机构信息

Angara Affiliated Department of East Siberian Center of Human Ecology, Siberian Division of the Russian Academy of Medical Sciences, Russia.

出版信息

Bull Exp Biol Med. 2013 Nov;156(1):15-8. doi: 10.1007/s10517-013-2266-2.

DOI:10.1007/s10517-013-2266-2

PMID:24319713

Abstract

The metabolic test with antipyrine was performed, the relationship between genotypes of GSTT1 and GSTM1 polymorphisms were studied, and cotinine level was measured in 116 men chronically exposed to mercury. The individuals were divided in 4 groups depending on the diagnosis of chronic mercury intoxication. The changes in the parameters of antipyrine test were studied in linked samples (N=62, 4 year interval); in patients with chronic mercury intoxication, the disease stage was taken into account. Inhibition of antipyrine metabolism, increased frequency of combination of GSTT1(0/0)/GSTM1(+) genotypes in patients with chronic mercury intoxication, and the specificity of cytochrome P450 inhibition with mercury suggest that disease progression is related to inhibition of cytochrome P450 isoforms in the brain that catalyze regulation of endogenous substrates.

摘要

对116名长期接触汞的男性进行了安替比林代谢试验，研究了谷胱甘肽S-转移酶T1（GSTT1）和谷胱甘肽S-转移酶M1（GSTM1）基因多态性的基因型之间的关系，并测定了可替宁水平。根据慢性汞中毒的诊断将个体分为4组。在关联样本（N = 62，间隔4年）中研究了安替比林试验参数的变化；在慢性汞中毒患者中，考虑了疾病阶段。慢性汞中毒患者中安替比林代谢受到抑制、GSTT1(0/0)/GSTM1(+)基因型组合频率增加以及汞对细胞色素P450的抑制特异性表明，疾病进展与大脑中催化内源性底物调节的细胞色素P450同工酶受到抑制有关。