砷接触工人尿甲基砷酸水平与P53基因损伤的关系

Relationship between P53 Gene Damage and Urinary Monomethylarsonic Acid Levels in Workers Exposed to Arsenic

  • 摘要:
    目的 观察砷职业暴露人群尿甲基砷酸水平与P53基因损伤的关系,深入认识砷的遗传毒性。

    方法 选取砒霜厂95名砷接触工人作为暴露组,另选对照组55人,采集外周血和晨尿。用氢化物发生原子吸收分光光度法检测尿中各形态砷化合物和总砷含量,并计算一、二级甲基化指数。实时荧光定量PCR扩增人群外周血淋巴细胞P53基因外显子5和8,通过循环阈值推算损伤后扩增效率,间接计算损伤指数。

    结果 暴露组工人尿中无机砷(iAs)、甲基砷酸(MMA)、二甲基砷酸(DMA)均明显高于对照组;暴露组工人二级甲基化指数明显低于对照组;暴露组工人P53基因外显子5和8的损伤指数均明显高于对照组;尿中砷一级甲基化指数与P53基因第5外显子损伤指数存在明显的正相关,尿中砷二级甲基化指数与P53基因第5外显子损伤指数存在明显的负相关。

    结论 职业砷暴露工人二级甲基化指数明显增加,体内存在较多甲基砷酸,可能是P53基因外显子5损伤的主要原因。

     

    Abstract:
    Objective To study the relationship between P53 gene damage and urinary monomethylarsonic acid levels in people occupationally exposed to arsenic, and to understand genotoxicity of arsenic.

    Methods Ninety-five workers exposed to arsenic in two arsenic plants were recruited as the exposure group, and 55 residents without arsenic exposure as the control group. Their peripheral blood and urina sanguinis were collected. Inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine were detected by hydride generation-atomic absorption spectrometry to calculate primary and secondary methylation indices. Exon 5 and 8 of P53 gene were amplified by real-time polymerase chain reaction to calculate efficiency of modified templates and damage index using cycle threshold.

    Results The concentrations of iAs, MMA and DMA in the exposure group were significantly higher than that in the controls. The secondary methylation index in the exposed population was significantly lower than in the controls. The damage index of exon 5 and 8 of P53 gene in the exposure group was significantly higher than that in the control group. A positive correlation was found between the damage index of exon 5 and the primary methylation index, and a negative one was found between the damage index of exon 5 and the secondary methylation index.

    Conclusion There is a significant effect of arsenic on secondary methylation index of arsenic-exposed workers. The results suggest that monomethylarsonic acid may play an important role in the damage of exon 5 of P53 gene.

     

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