The elucidative research of the factors which regulate the symptoms of chronic arsenic poisoning

慢性砷中毒症状调节因素的阐明性研究

• 批准号: 15406022
• 负责人: YOSHIDA Takahiko
• 金额: $ 7.3万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15406022/
• 关键词: arsenic poisoning; drinking water; hyperkeratosis of skin; dyspigmentation of skin; methylation; epidermal keratinocyte; dermal fibroblast; gender difference; 個体差; 中国; 細胞培養; 動物実験

We examined the relation between arsenic exposure and skin lesions in the residents who had been lived at naturally arsenic contaminated field and had been exposed to arsenic at various dose via drinking well water in Baotou county of Inner Mongolia, China. Odds ratio in prevalence of skin lesions especially of dyspigmentation was significantly higher in male residents. Ability to methylate arsenic ; 1st or 2nd methylation, estimated by measuring arsenic concentration with their chemical types in blood or urine from individual subjects was studied as being related to their skin lesions. Male showed lower ability of 2nd methylation compare with female. The cases with higher ability of 1st methylation and lower ability of 2nd methylation estimated with blood sample from both genders had heavier dyspigmentation. The cases with lower ability of 2nd methylation estimated with urine sample had heavier hyperkeratosis in palm and sole, and dyspigmentation. Odds ratios of prevalence of any skin … More lesions relating to chemical form of arsenic in blood adjusted with gender and age were the highest in monomethyl arsenic and the 2nd in dimethyl arsenic. In other words, the individual with less ability of 2nd than 1st methylation and resulted to accumulate monomethyl arsenic in their body had sever skin lesions, especially dyspigmentation. Significant improvement of skin lesions were observed in the first year after the changing drinking water to low arsenic, but the pace of improvement was slow in the ensuing years. There was no correlation between the ability of methylation and the improvement of skin lesions.Relatively low dose (1,4 and 8 micro M) of trivalent inorganic arsenic (sodium arsenite) enhanced the proliferation of normal human epidermal keratinocytes (NHEK) via production of GM-CSF and TGF-alpha by themselves. Increase of daughter chromosome exchange ratio was also observed in the NHEK culture with existence of arsenic. The proliferation of mouse dermal fibroblast (3T3) cells was induced by low dose of arsenic. The both enhancements of proliferation in epidermal keratinocyte and dermal fibroblast induced by arsenic were suggested to be association with hyperkeratosis observed in residents who had been exposed to arsenic via drinking water for long periods. Less

本文对内蒙古包头市自然砷污染区居民经饮水接触不同剂量砷后皮肤损害与砷暴露的关系进行了研究。男性居民中皮肤病变尤其是色素异常患病率的比值比显著较高。砷的甲基化能力;通过测量个体受试者血液或尿液中砷浓度及其化学类型来估计第一或第二甲基化，研究其与皮肤病变的关系。男性第二位甲基化能力低于女性。第一甲基化能力高、第二甲基化能力低的病例，其色素异常程度较重。尿二甲基化能力低者，掌跖角化程度重，色素异常。任何皮肤病患病率的比值比 ...更多信息 经性别和年龄调整后，与血中砷的化学形态有关的病变以一甲基砷最高，二甲基砷次之。换句话说，第二次甲基化能力低于第一次甲基化能力并导致体内积累一甲基砷的个体具有严重的皮肤病变，尤其是色素异常。在饮用水改为低砷后的第一年，观察到皮肤病变的显着改善，但在随后的几年中，改善的步伐缓慢。低剂量（1、4和8 μ M）的三价无机砷（亚砷酸钠）通过自身产生GM-CSF和TGF-α促进正常人表皮角质形成细胞（NHEK）的增殖。在含砷的NHEK培养物中，也观察到子体染色体交换率的增加。低剂量砷可诱导小鼠皮肤成纤维细胞（3 T3）增殖。砷引起的表皮角质形成细胞和真皮成纤维细胞增殖的增强与长期饮水接触砷的居民所观察到的角化过度有关。少