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[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。
[Objective] To observe the relationship between urine methyl-arsenic acid level and P53 gene injury in arsenic occupational exposure groups and to get a deeper understanding of the genotoxicity of arsenic. [Method] Ninety-five workers exposed to arsenic in arsenic-fixing cream factory were selected as the exposed group, while another 55 were selected as control group. Peripheral blood and morning urine were collected. The arsenic compounds and total arsenic in urine were detected by atomic absorption spectrophotometry and the first and second methylation indices were calculated. Real-time fluorescence quantitative PCR amplification of peripheral blood lymphocytes in patients with exon 5 and 8 of P53 gene, through the cycle threshold calculation of post-injury amplification efficiency, indirect calculation of injury index. [Results] The urinary inorganic arsenic (iAs), methyl arsenic acid (MMA) and dimethyl arsenate (DMA) in exposed group were significantly higher than those in control group. The secondary methylation index in exposed group was significantly lower than that in control group Group; Exposed group workers P53 gene exons 5 and 8 of the damage index were significantly higher than the control group; urinary arsenic methylation index and P53 gene exon 5 damage index there is a clear positive correlation between urine Arsenic two methylation index and P53 gene exon 5 damage index there is a significant negative correlation. [Conclusion] The secondary methylation index of occupational arsenic exposure workers increased significantly, more methyl arsenic acid was present in the body, which may be the main reason for the exon 5 damage of P53 gene.