摘要
目的 探讨职业砷暴露人群六个线粒体基因DNA损伤情况,并分析线粒体DNA损伤与尿砷及其代谢的关系.方法 于2017-2018年,选择云南某高污染砒霜厂78名工人为砷暴露组,选择附近村庄无砷接触史的24名居民为对照组,采用氢化物发生-原子吸收分光光度法测定人群尿中不同形态砷含量,采用实时荧光定量PCR方法检测人群外周血中ND1、ATP6、ATP8、COX1、COX2、COX3等六个线粒体基因DNA损伤水平.结果 砷暴露组尿中无机砷、一甲基胂酸、二甲基胂酸及总砷含量均显著高于对照组(P<0.05),一甲基胂酸和二甲基胂酸百分比显著高于对照组(P<0.05),二甲基化指数显著低于对照组(P<0.05).砷暴露组六个线粒体基因DNA损伤水平显著高于对照组(P<0.05).六个线粒体基因DNA损伤水平与尿中无机砷、一甲基胂酸、二甲基胂酸、一甲基胂酸百分比呈正相关(P<0.05),与二甲基胂酸百分比呈负相关(P<0.05).高二甲基化指数组的六个线粒体基因DNA损伤水平显著低于低二甲基化指数组(P<0.05).结论 职业砷暴露导致人群线粒体DNA损伤,线粒体DNA损伤与砷在机体内甲基化代谢能力有关.
Abstract
Objective To explore the relationship between DNA damage of six mitochondrial genesand urinary arsenic metabolism in workers exposed to arsenic.Methods The content of arsenic in the urine was determined by hydride generation-atomic absorption spectrophotometry,and the DNA damage levels of six mitochondrial genes(ND1,ATP6,ATP8,COX 1,COX2,COX3)in the peripheral blood were detected by real-time fluorescence quantitative PCR among occupational arsenic exposure workers in an arsenic factory in Yunnan(the exposure group,n=78)and population without history of arsenic exposure(the control group,n=24)from 2017 to 2018.Results The contents of inorganic arsenic,monomethyl arsenic,dimethylated arsenic,and total arsenic in the urine of the arsenic-exposed group were significantly higher than those in the control group(P<0.05).The percentage of dimethylated arsenic,dimethylated arsenic was significantly higher than that in the control group(P<0.05),while the dimethylation index was significantly lower than that in the control group(P<0.05).The DNA damage levels of the six mitochondrial genes in the occupational arsenic exposure group were significantly higher than those in thecontrol group(P<0.05).The damage levels of the six mitochondrial genes were positively correlated with inorganic arsenic,monomethyl arsenic,dimethylated arsenic,and the percentage of monomethyl arsenic in urine and negatively correlated with the percentage of dimethylated arsenic(P<0.05).The DNA damage levels of six mitochondrial genes in high SMI group were significantly lower than those in low SMI group(P<0.05).Conclusion Occupational arsenic exposure induces mitochondrial DNA damage,which is related to the methylation metabolism of arsenic in the body.
基金项目
云南省科技厅昆明医科大学应用基础研究联合专项(202101AY070001-054)
国家自然科学基金(82160607)
云南省科技厅基础研究专项-面上项目(202401AT070177)
昆明医科大学环境与职业砷暴露致癌研究科技创新团队(CXTD202201)