Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water
Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water
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DOI：
10.1002/ijc.21640
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发表时间：
2006-05-15
影响因子：
6.4
通讯作者：
Giri, AK
中科院分区：
文献类型：
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作者：
Ghosh, P;Basu, A;Giri, AK
在印度西孟加拉，30多万接触砷的人出现砷中毒症状，包括皮肤癌和各种内脏癌。由于只有1.5-20%的接触人群表现出砷诱导的皮肤病变，因此认为遗传变异可能在砷毒性和致癌性中起重要作用。本研究共招募了422名无关的砷暴露受试者（244名皮肤症状和178名无症状）。通过淋巴细胞染色体畸变和口腔粘膜细胞、尿路上皮细胞和双核淋巴细胞微核形成测定细胞遗传学损伤，对具有相似社会经济地位的未暴露、皮肤症状和无症状个体进行了研究。通过PCR扩增鉴定GSTT 1和GSTM 1基因的无效突变。采用PCR-RFLP方法检测与多种癌症易感性相关的GSTP 1单核苷酸多态性。有症状个体的细胞遗传学损伤水平高于无症状个体，无症状个体的遗传毒性显著高于未暴露个体。GSTT 1和GSTP 1的等位基因变异在这两组之间没有观察到差异。GSTMI无效基因频率的发生率在无症状组中显著较高。GSTM 1阳性（至少一个等位基因）的个体有明显更高的砷诱导皮肤病变的风险（比值比，1.73; 95%可信区间，1.24-2.22）。这些结果表明GSTM 1 null在砷毒性中具有保护作用。这项研究还表明，无症状的个体亚临床影响，也显着容易受到砷诱导的遗传毒性。(c)2005 Wiley-Liss，Inc.
In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 1.5-20% of the exposed population manifest arsenic-induced skin lesions, it Is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTMI null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity. (c) 2005 Wiley-Liss, Inc.