Chen Chien-Jen, Hsu Lin-I, Wang Chih-Hao, Shih Wei-Liang, Hsu Yi-Hsiang, Tseng Mei-Ping, Lin Yu-Chun, Chou Wei-Ling, Chen Chia-Yen, Lee Cheng-Yeh, Wang Li-Hua, Cheng Yu-Chin, Chen Chi-Ling, Chen Shu-Yuan, Wang Yuan-Hung, Hsueh Yu-Mei, Chiou Hung-Yi, Wu Meei-Maan
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, 1 Jen-Ai Road Section1, Taipei 10018, Taiwan, ROC.
Toxicol Appl Pharmacol. 2005 Aug 7;206(2):198-206. doi: 10.1016/j.taap.2004.10.023.
Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.
长期饮用含有无机砷的水会导致癌症和血管疾病，且存在剂量反应关系。台湾开展了一系列分子环境流行病学研究，以阐明砷相关健康危害的暴露、效应和易感性生物标志物。尿、发和指甲中的砷含量是短期（<1年）体内剂量的生物标志物，皮肤色素沉着和掌跖角化过度是长期（多年）体内剂量的生物标志物，尿中无机砷总代谢产物中一甲基胂酸的百分比可被视为生物有效剂量的暴露标志物。摄入无机砷的早期生物学效应生物标志物包括血液中活性氧化剂水平和抗氧化能力、炎症分子的基因表达，以及细胞遗传学变化，包括外周淋巴细胞的姐妹染色单体交换、微核和染色体畸变。在砷诱导和非砷诱导的移行细胞癌中，p53基因的突变类型和热点均存在显著差异。通过比较基因组杂交分析的染色体不平衡频率和杂合性缺失频率在砷诱导的移行细胞癌特定部位显著高于非砷诱导的移行细胞癌。砷诱导健康危害的易感性生物标志物包括参与外源性代谢、DNA修复和氧化应激的酶的基因多态性，以及血清类胡萝卜素水平。基因-基因和基因-环境相互作用通过包括基因组不稳定和氧化应激在内的毒理学机制参与砷诱导的健康危害。
