Chen Yongwen, Bai Yun, Yuan Jing, Chen Weihong, Sun Jianya, Wang Hong, Liang Huashan, Guo Liang, Yang Xiaobo, Tan Hao, Su Yougong, Wei Qingyi, Wu Tangchun
Institute of Occupational Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, Hubei 430030, People's Republic of China.
Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1703-7. doi: 10.1158/1055-9965.EPI-06-0291.
Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non-coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. We found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group (P < 0.001). Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys(554) variant genotype were higher than those with the AhR Arg(554)/Arg(554) genotype (P = 0.021). Similarly, the Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation.
越来越多的证据表明，多环芳烃（PAH）代谢产物引起的DNA损伤以及PAH代谢基因中的基因多态性均会导致个体对PAH诱导的致癌作用易感性增加。然而，PAH代谢基因中的基因多态性在暴露个体中的功能相关性仍不清楚。在这项针对240名焦炉工人（暴露组）和123名非焦炉工人（对照组）的研究中，我们采用PCR方法对芳烃受体（AhR）、细胞色素P450 1A1（CYP1A1）、谷胱甘肽S-转移酶M1（GSTM1）和谷胱甘肽S-转移酶T1（GSTT1）基因的多态性进行基因分型，并使用碱性彗星试验测定外周血淋巴细胞中的DNA损伤水平。我们发现，暴露组中经自然对数转换的橄榄尾矩（Olive TM）值显著高于对照组（P < 0.001）。此外，在暴露组中，具有AhR Lys（554）变异基因型的受试者的Olive TM值高于具有AhR Arg（554）/Arg（554）基因型的受试者（P = 0.021）。同样，具有CYP1A1 MspI CC + CT基因型的非焦炉工人的Olive TM值低于具有CYP1A1 MspI TT基因型的工人（P = 0.005）。然而，对于GSTM1和GSTT1，这些差异并不明显。这些结果表明，AhR的多态性可能会调节暴露组中PAHs的作用；然而，这种多态性可能影响PAH诱导的DNA损伤水平的潜在分子机制值得进一步研究。
