The Relationship between Arsenic Exposure and DNA Damage of EGFR，PTEN，Kras，and PIK3CA Genes in Arsenic Factory Workers
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摘要:
目的 探索砒霜厂职业砷暴露工人EGFR、PTEN、Kras、PIK3CA 4个基因DNA损伤与尿砷及其代谢的关系。 方法 选取云南某砒霜厂78名一线职业砷暴露工人为暴露组和24名无砷职业暴露史人群为对照组。通过实时荧光定量PCR（Q-PCR）的方法检测外周血淋巴细胞中EGFR、PTEN、Kras、PIK3CA 4个基因DNA损伤，检测所有工人尿中无机砷、一甲基胂酸、二甲基胂酸的含量并计算百分比。 结果 职业砷暴露组人群4个基因的DNA损伤以及平均损伤高于对照组（P < 0.05）。4个基因的平均损伤与尿中的无机砷、一甲基胂酸、二甲基胂酸、一甲基胂酸百分比呈正相关，与二甲基胂酸百分比呈负相关（P < 0.05）。 结论 砷暴露导致人群重要基因损伤、4个基因平均损伤具有作为损伤评估标志物的潜力。 Abstract:Objective To explore the relationship between DNA damage and urinary arsenic metabolism in four genes of EGFR, PTEN, Kras and PIK3CA in workers exposed to arsenic in arsenic factories. Methods A total of 78 first-line occupational arsenic exposure workers in an arsenic factory in Yunnan were selected as the exposure group and 24 people without history of arsenic exposure were included as the control group. The DNA damage of EGFR, PTEN, Kras and PIK3CA genes in peripheral blood lymphocytes was detected by real-time fluorescence quantitative PCR, and the contents of inorganic arsenic, monomethyl arsine acid and dimethylamine in the urine of all workers were detected and the percentages were calculated. Results The DNA damage and mean damage of the four genes in the occupational arsenic exposure group were significantly higher than those in the control group （P < 0.05）. The mean damage of the four genes was positively correlated with inorganic arsenic, monomethyl arsine acid, dimethylamine acid, and the percentage of monomethyl arsine in urine and negatively correlated with the percentage of dimethylamine （P < 0.05）. Conclusion The damage of important genes caused by arsenic exposure and the average damage of four genes have the potential to be used as markers of damage assessment. -
表 1 受试人群的一般特征和尿砷水平（
$ \bar{x} \pm s $ ）Table 1. General characteristics and urinary arsenic levels of the test population （
$ \bar{x} \pm s $ ）变量 对照组（n = 24） 暴露组（n = 78） t P 年龄（岁） 35.814 ± 3.241 36.531 ± 5.972 / / 吸烟（是/否） 14/10 46/32 / / 饮酒 （是/否） 11/13 38/40 / / iAs 0.439 ± 0.185 2.023 ± 0.464 16.291 < 0.001* MMA 0.379 ± 0.153 2.141 ± 0.489 17.355 < 0.001* DMA 1.124 ± 0.304 2.660 ± 0.516 13.824 < 0.001* iAs% 13.763 ± 11.392 17.457 ± 12.409 1.299 0.197 MMA% 8.531 ± 2.322 19.150 ± 5.071 9.921 < 0.001* DMA% 77.712 ± 12.001 63.393 ± 12.291 −5.019 < 0.001* PMI 1.166 ± 1.290 1.614 ± 1.289 1.488 0.140 SMI 10.010 ± 3.777 3.763 ± 2.126 −10.291 < 0.001* *P < 0.05。 
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表 2 受试人群的4个基因的损伤和平均损伤的比较（
$ \bar{x} \pm s $ ）Table 2. Comparison of damage and average damage of 4 genes in the test population （
$ \bar{x} \pm s $ ）变量 对照组
（n = 24）暴露组
（n = 78）损伤变化 t P EGFR 2.299 ± 0.118 2.514 ± 0.047 0.215 2.024 0.046* PTEN 2.432 ± 0.078 2.791 ± 0.065 0.359 2.884 0.005* Kras 2.468 ± 0.124 2.818 ± 0.060 0.350 2.718 0.008* PIK3CA 2.852 ± 0.061 3.225 ± 0.038 0.373 4.856 < 0.001* 平均损伤 2.512 ± 0.075 2.837 ± 0.036 0.325 4.181 < 0.001* *P < 0.05。
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表 3 3种砷化物含量与所有受试者基因DNA损伤水平的相关性
Table 3. Correlation between the levels of three arsenicals and the levels of genetic DNA damage in all subjects
DNA 损伤 iAs MMA DMA r P r P r P EGFR 0.160 0.109 0.157 0.116 0.112 0.263 PTEN 0.235 0.018* 0.237 0.016* 0.185 0.063 Kras 0.182 0.068 0.200 0.044* 0.137 0.170 PIK3CA 0.324 0.001* 0.319 0.001* 0.269 0.006* 平均损伤 0.296 0.003* 0.302 0.002* 0.230 0.020* 数据分析采用皮尔逊相关法，*P < 0.05。
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表 4 3种砷化物尿中的百分比与所有受试者基因DNA损伤水平的相关性
Table 4. 3 Correlation between percentages of arsenic compounds in urine and levels of genetic DNA damage in all subjects
DNA损伤 iAs% MMA% DMA% r P r P r P EGFR 0.086 0.388 0.249 0.012* −0.177 0.076 PTEN 0.059 0.554 0.319 0.001* −0.185 0.063 Kras 0.110 0.269 0.354 < 0.001* −0.241 0.015* PIK3CA 0.121 0.224 0.329 0.0001* −0.240 0.015* 平均损伤 0.125 0.210 0.427 < 0.001* −0.285 0.004* 数据分析采用皮尔逊相关法，*P < 0.05。
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表 5 所有受试者按SMI水平分层的DNA损伤比较（
$ x \pm s $ ）Table 5. Comparison of DNA damage stratified at SMI level for all subjects （
$\bar x \pm s $ ）变量 低SMI（n = 51） 高SMI（n = 51） t P SMI[中位数（范围）] 2.654 （1.064-3.800） 7.444 （3.848-21.840） / / EGFR 2.550 ± 0.065 2.377 ± 0.063 1.914 0.059 PTEN 2.811 ± 0.083 2.602 ± 0.070 1.932 0.056 Kras 2.874 ± 0.081 2.596 ± 0.074 2.537 0.013* PIK3CA 3.252 ± 0.055 3.022 ± 0.042 3.345 0.001* 平均损伤 2.872 ± 0.049 2.649 ± 0.047 3.282 0.001* *P < 0.05。
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