Aberrant promoter methylation of p16INK4a and O6-methylguanine-DNA methyltransferase genes in workers at a Chinese uranium mine

Aberrant promoter methylation of p16INK4a and O6-methylguanine-DNA methyltransferase genes in workers at a Chinese uranium mine
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DOI:
10.1539/joh.48.261
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发表时间:
2006-07-01
影响因子:
3
通讯作者:
Tong, Jian
Tong, Jian
中科院分区:
医学4区
文献类型:
--
作者:
Su, Shibiao;Jin, Yali;Tong, Jian

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目的:探讨p16(INK 4a)基因甲基化与O-6-甲基鸟嘌呤-DNA甲基转移酶(O-6-Methylguanine-DNA Methyltransferase,O-6-Methylguanine-DNA Methyltransferase,O-6-Methylguanine-DNA Methyltransferase)的关系用O-6-MGMT法测定了某铀矿91名男性矿工的职业氡暴露量,按氡累积暴露剂量(2 ~ 425 WLM)分为4组(工作水平月),并通过特异性PCR检测确定痰液样本中p16(INK 4a)和O-6-MGMT基因的异常启动子甲基化。结果表明,随着氡累积剂量的增加,p16(INK 4a)基因(z=2.844,P=0.005)和O-6-MGMT基因(z=3.034,P=0.002)的甲基化率以及两个基因的总甲基化率(z=3.859,P=0.0001)均显著增加。这种甲基化可以作为一种潜在的标记,用于检测职业性氡暴露引起的早期DNA损伤。
To find the possible association of gene methylation of p16(INK4a) and O-6-Methylguanine-DNA Methyltransferase (O-6-MGMT) with occupational exposure to radon, 91 male miners from a uranium mine in China were divided into 4 groups according to the cumulative doses of radon exposure from 2 to 425 WLM (working-level months), and aberrant promoter methylation of p16(INK4a) and O-6-MGMT genes in sputum samples was determined by a specific PCR assay. The results revealed that the methylated rates of p16(INK4a) gene (z=2.844, P=0.005) and O-6-MGMT gene (z=3.034, P=0.002), and the total methylated rate of these two genes (z=3.859, P=0.0001) increased significantly with the cumulative doses of radon among the miners. This methylation could be applied as a potential marker for the detection of early DNA damage induced by occupational radon exposure.