Molecular toxicology

人类活动，如化石燃料消耗和金属开采，已导致环境日益受到环境持久性有毒重金属和类金属化合物的污染。这些污染物的人为排放可能会进一步增加，因为印度和中国等人口众多的国家将增加化石燃料消费，以提高生活水平。因此，人类从饮食中摄入的无机和有机形式的砷、镉、铅和汞的含量不断增加，引起了公众的极大关注。毒理学研究通过研究单一金属和类金属对动物的影响来解决人类对这些污染物的暴露问题，并为我们提供了有关其急性毒性的宝贵数据，如毒性机制和哺乳动物靶器官。然而，对有毒金属和类金属化合物在哺乳动物中的慢性毒性和致癌性的分子基础知之甚少。这必须归因于这样一个事实，即在吸收特定的有毒金属或类金属化合物进入血流后发生的生物转化知之甚少。应用两种先进的光谱技术，我们将从结构上表征迄今未知的金属和含类金属的代谢物，这些代谢物在血液中形成，并与金属和类金属的慢性毒性密切相关，可能与人类疾病有关，如帕金森病和自闭症。这种方法将使我们能够更好地确定多种金属和类金属暴露对人类健康的影响。此外，这项研究将揭示重要的哺乳动物解毒机制，这是开发治疗金属和类金属化合物慢性毒性的关键，目前影响数百万人。

Human activities, such as fossil fuel consumption and metal mining, have caused the environment to be increasingly contaminated with environmentally persistent toxic heavy metal and metalloid compounds. The anthropogenic emissions of these pollutants are likely to increase even further as populous countries, such as India and China will increase their fossil fuel consumption in order to improve their standard of living. The resulting exposure of humans to increasing dietary levels of inorganic and organic forms of arsenic, cadmium, lead and mercury is therefore of much public concern. Toxicological studies have addressed the exposure of humans to these pollutants by studying the effect of single metals and metalloids in animals and have provided us with valuable data concerning their acute toxicity, such as the mechanism of toxicity and the mammalian target organs. Considerably less, however, is known about the molecular basis of the chronic toxicity and carcinogenicity of toxic metals and metalloid compounds in mammals. This must be attributed to the fact that biotransformations that occur after the absorption of a particular toxic metal or metalloid compound into the blood stream are poorly understood. Applying two advanced spectroscopic techniques, we will structurally characterize hitherto unknown metal and metalloid-containing metabolites which are formed in blood and are critically involved in the chronic toxicity of metals and metalloids and may be involved in human diseases, such as Parkinson's Disease and autism.This approach will allow us to better define the effect of multiple metal and metalloid exposure on human health. In addition, this research will reveal important mammalian detoxification mechanisms which are the key to develop a treatment against the chronic toxicity of metals and metalloid compounds which currenty affects millions of people.