Xu Yuanyuan, Wang Yi, Zheng Quanmei, Li Xin, Li Bing, Jin Yaping, Sun Xiance, Sun Guifan
Department of Occupational and Environmental Health, College of Public Health, China Medical University, Heping District, Shenyang, PR China.
Toxicol Appl Pharmacol. 2008 Oct 1;232(1):142-9. doi: 10.1016/j.taap.2008.06.010. Epub 2008 Jul 1.
Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.
尽管氧化应激被认为是砷的一种重要致病机制，并且砷甲基化能力被认为与砷相关疾病密切相关，但砷甲基化能力与砷诱导的氧化应激之间的关联仍不清楚。为了探究氧化应激及其与砷甲基化的关联，我们对208名高砷暴露和59名低砷暴露受试者进行了横断面研究。通过氢化物发生原子吸收光谱法测定尿中砷形态[无机砷（iAs）、一甲基砷（MMA）和二甲基砷（DMA）]的水平。尿中砷形态的比例、首次甲基化率（FMR）和二次甲基化率（SMR）被用作砷甲基化能力的指标。通过酶联免疫吸附测定试剂盒分析尿中8-羟基-2'-脱氧鸟苷（8-OHdG）的浓度。测定全血中还原型谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性以反映抗氧化状态。与低暴露的儿童和成人相比，高砷暴露的儿童和成人尿中8-OHdG浓度显著升高，但血中GSH水平降低。在多元线性回归模型中，砷暴露儿童和成人的血中GSH水平和尿中8-OHdG浓度与尿中砷形态水平显示出强烈关联。尿中砷形态、FMR或SMR比例处于较低和较高四分位数的砷暴露受试者在尿8-OHdG、血GSH和SOD方面存在显著差异。在多变量回归分析中也观察到了砷甲基化能力与8-OHdG、GSH和SOD之间的关联。这些结果可能为人类砷甲基化能力与氧化应激之间提供联系，并表明砷诱导的不良健康影响通过氧化应激与砷甲基化有关。
