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评价暴露于甲基汞的亚马逊人群中谷胱甘肽 S-转移酶 GSTM1 和 GSTT1 多态性和甲基汞代谢。

Evaluation of glutathione S-transferase GSTM1 and GSTT1 polymorphisms and methylmercury metabolism in an exposed Amazon population.

机构信息

Department of Clinical, Toxicological and Bromatological Analyses, School of Phamaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

J Toxicol Environ Health A. 2012;75(16-17):960-70. doi: 10.1080/15287394.2012.695232.

Abstract

Over the last decades, the presence of methylmercury (MeHg) in the Amazon region of Brazil and its adverse human health effects have given rise to much concern. The biotransformation of MeHg occurs mainly through glutathione (GSH) in the bile mediated by conjugation with glutathione S-transferases (GST). Epidemiological evidence has shown that genetic polymorphisms may affect the metabolism of MeHg. The aim of this study was to evaluate the association between GST polymorphisms, GSH, and Hg levels in blood (B-Hg) and in hair (H-Hg) of an Amazon population chronically exposed to the metal through fish consumption. Blood and hair samples were collected from 144 volunteers (71 men, 73 women). B-Hg and H-Hg levels were determined by inductively coupled plasma-mass spectrometry, and GSH levels were evaluated by a spectrophotometric method. GSTM1 and T1 genotyping evaluation were carried out by multiplex polymerase chain reaction (PCR). Mean levels of B-Hg and H-Hg were 37.7 ± 24.5 μg/L and 10.4 ± 7.4 μg/g, respectively; GSH concentrations ranged from 0.52 to 2.89 μM/ml of total blood. Distributions for GSTM1/T1, GSTM1/GSTT10, GSTM10/T1, and GSTM10/GSTT10 genotypes were 35.4, 22.2, 25.0, and 17.4%, respectively. GSTT1 genotype carriers presented lower levels of B-Hg and H-Hg when compared to other genotypes carriers. In addition, GSTM10/GSTT10 individuals presented higher Hg levels in blood and hair than subjects presenting any other genotypes. There appeared to be no evidence of an effect of polymorphisms on GSH levels. Therefore, our data suggest that GST polymorphisms may be associated with MeHg detoxification.

摘要

在过去的几十年里,巴西亚马逊地区甲基汞(MeHg)的存在及其对人类健康的不良影响引起了广泛关注。MeHg 的生物转化主要通过胆汁中的谷胱甘肽(GSH)与谷胱甘肽 S-转移酶(GST)结合来完成。流行病学证据表明,遗传多态性可能会影响 MeHg 的代谢。本研究旨在评估 GST 多态性与长期通过鱼类摄入金属而接触该金属的亚马逊地区人群的血液(B-Hg)和头发(H-Hg)中 GSH 和 Hg 水平(B-Hg 和 H-Hg)之间的关系。从 144 名志愿者(71 名男性,73 名女性)中采集血液和头发样本。通过电感耦合等离子体质谱法测定 B-Hg 和 H-Hg 水平,通过分光光度法评估 GSH 水平。通过多重聚合酶链反应(PCR)进行 GSTM1 和 T1 基因分型评估。B-Hg 和 H-Hg 的平均水平分别为 37.7±24.5μg/L 和 10.4±7.4μg/g;全血中 GSH 浓度范围为 0.52-2.89μM/ml。GSTM1/T1、GSTM1/GSTT10、GSTM10/T1 和 GSTM10/GSTT10 基因型的分布分别为 35.4%、22.2%、25.0%和 17.4%。与其他基因型携带者相比,GSTT1 基因型携带者的 B-Hg 和 H-Hg 水平较低。此外,GSTM10/GSTT10 个体的血液和头发中的 Hg 水平高于其他任何基因型的个体。似乎没有证据表明多态性对 GSH 水平有影响。因此,我们的数据表明 GST 多态性可能与 MeHg 解毒有关。

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