Biological fate of arsenic species

砷形态的生物归宿

• 批准号: 6577205
• 负责人: H VASKEN APOSHIAN
• 金额: $ 14.22万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577205
• 关键词: animal tissue; arsenic; cell line; environmental contamination; environmental health; environmental toxicology; enzyme activity; enzyme mechanism; glutathione; hazardous substances; human tissue; metal metabolism; tissue /cell culture; toxin metabolism

The biochemical fate of inorganic arsenate and arsenite and their biotransformants are the major interest of this laboratory. Elucidation of the fate of inorganic arsenic in mammals would be expected to lead to a better understanding of the mechanisms of chronic inorganic arsenic poisoning, which is an ongoing public health problem in many countries, such as India, China, Chile, Mexico, Bangladesh, Inner Mongolia, Argentina and Taiwan and a potential one in the United States. Inorganic arsenic in the drinking water of millions of people has become a problem of global proportions. Populations are drinking water containing levels of arsenic that far exceed the maximum contamination levels established by World Health Organization and the United States EPA. Arsenic is a carcinogen for humans. Yet, how the human and other mammals process and detoxify the toxic inorganic forms of arsenic is still beset by conflicting reports, ambiguities and unknowns. This laboratory plans to study the enzymes in the human body that modifies the toxicity of arsenic species. This will be done by purifying these enzymes and studying their molecular mechanisms of action. Inhibitors of this process will also be sought as a possible way to block conversion to any carcinogenic biotransformant. A compound of high concentration is the cell is glutathione and it is known to form complexes with arsenic species. We shall study these complexes and determine the role of glutathione in how arsenic species efflux the cell.

无机砷酸盐和亚砷酸盐及其生物转化体的生化命运是本实验室的主要研究方向。数百万人饮用水中的无机砷已经成为一个全球性的问题。人们饮用的砷含量远远超过世界卫生组织和美国环境保护署确定的最大污染水平。砷是人类的致癌物。然而，人类和其他哺乳动物如何处理和解毒有毒无机形式的砷仍然受到相互矛盾的报道、含糊不清和未知因素的困扰。该实验室计划研究人体中能够改变砷毒性的酶。这将通过纯化这些酶并研究它们的分子作用机制来完成。这一过程的抑制剂也将被寻求作为一种可能的方法来阻止转化为任何致癌的生物转化。细胞中的一种高浓度化合物是谷胱甘肽，已知它能与砷形成复合物。我们将研究这些复合物，并确定谷胱甘肽在砷物质如何流出细胞中的作用。