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Analysis of toxicity by organic halogens with in vivo ESR and transgenic mice

体内ESR和转基因小鼠有机卤素毒性分析

基本信息

批准号：
10470498
负责人：
UTSUMI Hideo
金额：
$ 7.87万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Environmental fields, such as river water, lake water, are contaminated with trihalo-methane, total organic halogen compounds, pre-dioxins and so on. Recently, it was reported in in vitro experiments, that generation of reactive oxygen species and/or nitric oxide affects redox regulation, and that such disorder of redox regulation participates in toxicities of these organic halogen compounds. In in vivo, antioxidant systems establish complicated radical-radical interactions and redox regulations. These facts indicated that in vivo toxicity of organic halogen compounds is different from that observed in in vitro experiments. It is therefore very important to measure disorder of in vivo redox directly.Electron spin resonance spectroscopy (ERS) is a unique method to measure unpaired electron spin. We have reported in vivo generation of bioradicals in several disease models of mice with in vivo ERS apparatus using nitroxyl radicals as radical probes. Measurements of changes in in vivo redox by organic halogen compounds using transgenic mice model of antioxidant, would clarify the mechanisms of toxicity of these halogen compounds in molecular level.Transgenic mice used in these experiments are bred in our laboratory. Breeding of transgenic mice of antioxidant was very difficult since probability of mating and numbers of littermates was fewer than that of nontransgenic mice. The result of project is now submitted to a journal.

三卤甲烷、总有机卤素化合物、前二恶英等污染物在河流、湖泊等环境领域中广泛存在，近年来有研究表明，活性氧和一氧化氮的产生影响氧化还原调节，而这种氧化还原调节的紊乱参与了这些有机卤素化合物的毒性。在体内，抗氧化系统建立复杂的自由基-自由基相互作用和氧化还原调节。这些事实表明，有机卤素化合物在体内的毒性是不同的，在体外实验中观察到的。电子自旋共振谱（ERS）是一种独特的测量未成对电子自旋的方法。我们已经报道了在体内产生的生物自由基在几种疾病模型的小鼠体内ERS装置使用硝酰基自由基作为自由基探针。利用抗氧化剂转基因小鼠模型测定有机卤素化合物在体内氧化还原的变化，将从分子水平上阐明这些卤素化合物的毒性机制。抗氧化剂转基因小鼠的繁殖非常困难，因为其交配概率和同窝仔数都低于非转基因小鼠。该项目的成果现已提交给一份期刊。