铅作业工人遗传损伤与相关基因甲基化的关系  

Association between Genetic Damage and Methylation of Related Genes in Lead-Exposed Workers

作　　者：黄靖雯[1] 王佳珺 于立博[1] 张亚南[1] 郑国巧 吴炜 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院职业卫生与毒理学教研室,上海200032 [2]上海市化工职业病防治院体检科,上海200041

出　　处：《环境与职业医学》2016年第1期1-6,共6页Journal of Environmental and Occupational Medicine

摘　　要：[目的]探讨铅作业工人遗传损伤与相关基因启动子区域甲基化的情况。[方法]采用胞质分裂阻滞微核试验评估44名铅作业工人和50名非铅作业对照组工人染色体损伤水平,应用甲基化特异性聚合酶链反应检测δ-氨基-γ-酮戊酸脱水酶(ALAD)、O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、乳腺癌易感基因(BRCA1)3个基因的启动子区域甲基化水平。[结果]铅接触组微核率[(6.9±2.9)‰]明显高于对照组[(2.8±1.9)‰],差异具有统计学意义(P<0.001);铅接触组ALAD、BRCA1基因甲基化阳性率(分别为27%、80%)明显高于对照组(分别为6%、34%),差异具有统计学意义(P<0.05),OR分别为5.88、7.55;铅接触组ALAD、MGMT、BRCA1 3个基因中,甲基化组微核率[分别为(8.5±2.2)‰、(7.5±2.4)‰、(7.4±2.8)‰]明显高于非甲基化组[分别为(6.3±3.0)‰、(5.3±3.6)‰、(4.8±2.8)‰],差异具有统计学意义(P<0.05),率比分别为1.34、1.42、1.55。[结论]铅接触能致作业工人染色体损伤。铅作业工人中ALAD、MGMT、BRCA1 3个基因发生甲基化者的染色体损伤明显高于非甲基化者,提示上述基因的高甲基化状态与铅所致染色体损伤有关。［Objective］ To explore the association of genetic damage and methylation in promoter region of related genes in lead-exposed workers. ［Methods］ Cytokinesis-block micronucleus assay was conducted to detect the chromosomal damage of peripheral lymphocytes in 44 lead-exposed workers and 50 non-lead-exposed control workers. Methylation specific polymerase chain reaction was used to measure the methylation status in promoter regions of delta-aminolevulinic acid dehydratase （ALAD）, O6-methylguanine DNA methyltransferase （MGMT）, and breast cancer 1 （BRCA1）. ［Results］ The micronucleus frequency of the exposed group [（6.9±2.9）‰] was significantly higher than that of the control group [（2.8±1.9）‰] （P 〈 0.001）. Compared with the control group （6% and 34%, respectively）, the methylation rates of ALAD and BRCA1 （27% and 80% respectively） in the leadexposed group were significantly higher, with the ORs being 5.88 and 7.55 respectively （P 〈 0.05）. The micronucleus frequencies for ALAD, MGMT, and BRCA1 of the methylation subgroup [（8.5±2.2） ‰ , （7.5±2.4） ‰ , and （7.4±2.8） ‰ , respectively] were significantly higher than those of the non-methylation subgroup [（6.3±3.0）‰, （5.3±3.6）‰, and （4.8±2.8）‰, respectively] in the lead-exposed workers, with the frequency ratios being 1.34, 1.42, and 1.55, respectively （P 〈 0.05）. ［Conclusion］ Occupational exposure to lead could result in chromosomal damage. Chromosomal damage is higher in workers with higher methylation of ALAD, MGMT, and BRCA1, which indicates that methylation status might be associated with chromosomal damage induced by lead.

关 键 词：铅 胞质分裂阻滞微核试验 甲基化特异性聚合酶链反应 δ-氨基-γ-酮戊酸脱水酶 O6-甲基鸟嘌呤-DNA甲基转移酶 乳腺癌易感基因 

分 类 号：R135.11[医药卫生—劳动卫生]