School of Chinese Material Medica, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
School of Public Health, Kunming Medical University, Kunming, Yunnan, China.
Toxicol Ind Health. 2021 Dec;37(12):727-736. doi: 10.1177/07482337211013321. Epub 2021 Nov 3.
Epidemiological evidence suggests that the metabolic profiles of each individual exposed to arsenic (As) are related to the risk of cancer, coronary heart disease, and diabetes. The arsenite methyltransferase () gene plays a key role in As metabolism. Several single nucleotide polymorphisms in the gene may affect both enzyme activity and gene transcription. polymorphisms are associated with the proportions of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) in urine as well as the incidence of cancer. P21 protein is a cyclin-dependent kinase inhibitor. Mutations of the gene have been found in cancer patients. In our study, we investigate whether polymorphisms of the gene alter As methylation capacity and adversely affect the gene in arsenic trioxide plant workers. The DNA damage was examined by the quantitative polymerase chain reaction. Restriction fragment length polymorphism was used to analyze the genotype of the gene. The results showed that DNA damage in gene fragments was greater in those individuals exposed to high levels of As. There was a strong positive correlation between the DNA damage to gene fragments and the percentage of MMA in urine. However, DNA damage in gene fragments was negatively associated with the percentage of DMA in urine (%uDMA), primary methylation index (PMI), and secondary methylation index. We found that subjects with the rs7085104 GG or GA allele were associated with higher %uDMA and PMI and less DNA damage. The subjects with the rs11191454 GG+GA or GA allele were also associated with higher %uDMA and PMI and less DNA damage. Our results suggest that rs1191454 and rs7085104 in the gene affect the As-induced DNA damage by altering individual metabolic efficiency.
流行病学证据表明，个体暴露于砷（As）的代谢特征与癌症、冠心病和糖尿病的风险有关。亚砷酸甲基转移酶（）基因在 As 代谢中起着关键作用。基因中的几个单核苷酸多态性可能同时影响酶活性和基因转录。基因多态性与尿中单甲基砷酸（MMA）和二甲基砷酸（DMA）的比例以及癌症的发病率有关。P21 蛋白是一种细胞周期蛋白依赖性激酶抑制剂。已在癌症患者中发现基因的突变。在我们的研究中，我们研究了基因的多态性是否改变了 As 的甲基化能力，并对三氧化二砷厂工人的基因产生不利影响。通过定量聚合酶链反应检测 DNA 损伤。采用限制性片段长度多态性分析基因的基因型。结果表明，暴露于高水平 As 的个体中基因片段的 DNA 损伤更大。基因片段的 DNA 损伤与尿中 MMA 的百分比之间存在强烈的正相关。然而，基因片段的 DNA 损伤与尿中 DMA 的百分比（%uDMA）、初级甲基化指数（PMI）和次级甲基化指数呈负相关。我们发现，rs7085104 GG 或 GA 等位基因的个体与较高的%uDMA 和 PMI 以及较少的 DNA 损伤有关。rs11191454 GG+GA 或 GA 等位基因的个体也与较高的%uDMA 和 PMI 以及较少的 DNA 损伤有关。我们的研究结果表明，基因中的 rs1191454 和 rs7085104 通过改变个体代谢效率影响 As 诱导的 DNA 损伤。
