摘 要: 目的 研究铅暴露工人相关基因甲基化与遗传损伤的关系,从而探讨铅致遗传损伤的机制。方法 选择50名铅暴露工人和30名非铅暴露工人,应用胞质分裂阻滞微核试验(CBMN)和彗星试验检测工人遗传损伤情况,应用甲基化特异性PCR(MSP)检测ALAD、MGMT、hMLH1,BRCA1 4个基因启动子区的甲基化状态。结果 铅暴露组微核细胞率、彗尾长度均大于对照组,差异有统计学意义(P<0.05),且微核细胞率有随着血铅水平升高而升高的趋势(P<0.05);彗星发生率在血铅400~600μg/L组及>600μg/L组与对照组相比差异有统计学意义(P<0.05)。铅暴露组ALAD、MGMT、hMLHl、BRCA1基因启动子区甲基化阳性率均高于对照组,差异具有统计学意义(P<0.001);上述4个基因发生甲基化者的微核细胞率显著高于未发生甲基化者(P<0.05)。结论 铅暴露可引起工人遗传损伤,且血铅水平越高损伤越重。上述4个基因甲基化阳性率与铅暴露工人的遗传损伤程度有明显关联性。 |
关键词: 铅暴露 彗星试验 胞质分裂阻滞微核试验(CBMN) 遗传损伤 甲基化特异性PCR(MSP) |
中图分类号: R135.ll;R994
文献标识码: A
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基金项目: 沈阳市科技局人口与健康应用技术研究计划项目(18-014-4-58) |
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Study on relationship between methylation of related gene and genetic damage in lead-exposed workers |
HE Yang,WANG Kai,PANG Yan,ZHANG Yao-yao,ZHENG Xiao-mei,PENG Shan-zhuo
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The Ninth People's Hospital of Shenyang/Shenyang Institute of Occupational Health and Medicine,Shenyang 110024,China
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Abstract: Objective To investigate the relationship between methyation of related gene and genetic damage in lead exposed workers,so as to explore the mechanism of genetic damage caused by lead.Methods 50 lead exposed workers and 30 workers without lead were selected as subjects,cytokinesis-block micronucleus assay(CBMN)and comet assay were used for the detection of genetic damage,while the methylation status of promoter regions of aminolevulinic acid dehydratase (ALAD),O6-methylguanine-DNA methyltransferase(MGMT),human mismatch repair gene 1(hMLH1)and breast cancer susceptibility
gene(BRCA1)was detected by methylation-specific PCR(MSP).Results The results showed that the micronucleus rate and comet tail length of lead exposed group were higher than those of control group (P<0.05),and the micronucleus rate increased with the rise of blood lead level(P<0.05);the comet incidence in the blood lead 400~600μg/L group and the blood lead value >600μg/L group were all significantly higher than that of control group(P<0.05).The positive rates of methylation in promoter region of ALAD,MGMT,hMLH1 and BRCA1 gene in lead exposed group were higher than that of control group(P<0.001)as well,meanwhile,the rate of micronucleus cells in methylated group was significantly higher than that of unmethylated group(P<0.05).Conclusion Lead exposure can cause genetic damage in workers,and the higher the blood lead level,the severer the genetic damage,which suggested that the positive rates of methylation in four genes mentioned above was closely related to the degree of DNA damage in lead exposed workers. |
Keywords: lead exposure comet assay cytokinesis-block micronucleus assay(CBMN) genetic damage methylation-specific PCR(MSP) |