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

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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.