Chiou H Y, Hsueh Y M, Hsieh L L, Hsu L I, Hsu Y H, Hsieh F I, Wei M L, Chen H C, Yang H T, Leu L C, Chu T H, Chen-Wu C, Yang M H, Chen C J
School of Public Health, Taipei Medical College, Taiwan.
Mutat Res. 1997 Jun;386(3):197-207. doi: 10.1016/s1383-5742(97)00005-7.
In order to elucidate the relationships among arsenic methylation capacity, body retention, and genetic polymorphisms of glutathione S-transferase (GST) M1 and T1, a total of 115 study subjects were recruited from Lanyang Basin located on the northeast coast of Taiwan. Specimens of drinking water, blood, urine, hair and toenail were collected from each study subject. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic absorption spectrometry. Arsenic concentration in hair and toenail were quantitated by atomic absorption spectrophotometry. The polymerase chain reaction was used to determine genetic polymorphisms of GST M1 and T1. Arsenic concentrations in urine, hair, and toenail of study subjects were positively correlated with arsenic levels in their drinking water. Percentages of various arsenic species in urine (mean +/- standard error (SE) were 11.8 +/- 1.0, 26.9 +/- 1.2 and 61.3 +/- 1.4, respectively, for inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Men and women had similar arsenic methylation capability. No associations were observed between arsenic methylation capability and arsenic content in either drinking water or urine. Ratios of arsenic contents in hair and toenail to urinary arsenic content (mean +/- standard error) were 6.2 +/- 0.7 and 16.5 +/- 1.7, respectively. Genetic polymorphisms of GST M1 and T1 were significantly associated with arsenic methylation. Subjects having the null genotype of GST M1 had an increased percentage of inorganic arsenic in urine, while those with null genotype of GST T1 had an elevated percentage of DMA in urine. Arsenic contents in hair and toenail were significantly correlated with the increase in arsenic concentrations of drinking water and urine, while no significant associations were observed between arsenic contents in hair and toenail and polymorphisms of GST M1 and T1. The relationship between arsenic methylation capability and body retention was modified by genetic polymorphisms of GST M1 and T1. Arsenic contents in hair and toenail were negatively associated with MMA percentage and positively associated with DMA percentage among subjects having null genotypes of GST M1 and T1, but not among those with non-null genotypes.
为了阐明砷甲基化能力、体内蓄积量与谷胱甘肽S-转移酶（GST）M1和T1基因多态性之间的关系，从台湾东北海岸的兰阳溪流域招募了115名研究对象。采集了每位研究对象的饮用水、血液、尿液、头发和趾甲样本。采用高效液相色谱结合氢化物发生原子吸收光谱法对尿中无机砷和甲基化砷进行形态分析。用原子吸收分光光度法定量头发和趾甲中的砷浓度。采用聚合酶链反应确定GST M1和T1的基因多态性。研究对象尿、头发和趾甲中的砷浓度与他们饮用水中的砷水平呈正相关。尿中各种砷形态的百分比（平均值±标准误），无机砷、一甲基胂酸（MMA）和二甲基胂酸（DMA）分别为11.8±1.0、26.9±1.2和61.3±1.4。男性和女性具有相似的砷甲基化能力。未观察到砷甲基化能力与饮用水或尿液中砷含量之间存在关联。头发和趾甲中砷含量与尿砷含量的比值（平均值±标准误）分别为6.2±0.7和16.5±1.7。GST M1和T1的基因多态性与砷甲基化显著相关。GST M1基因缺失型的研究对象尿中无机砷百分比增加，而GST T1基因缺失型的研究对象尿中DMA百分比升高。头发和趾甲中的砷含量与饮用水和尿液中砷浓度的增加显著相关，而未观察到头发和趾甲中的砷含量与GST M1和T1基因多态性之间存在显著关联。GST M1和T1的基因多态性改变了砷甲基化能力与体内蓄积量之间的关系。在GST M1和T1基因缺失型的研究对象中，头发和趾甲中的砷含量与MMA百分比呈负相关，与DMA百分比呈正相关，但在非基因缺失型的研究对象中并非如此。
