New evaluation system of cell damage caused by environmental chemicals that effect lifestyle diseases

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1.Cytotoxicity of phenanthraquinone contained in diesel exhaust particlesPhenanthraquinone showed strong toxicity to cultured human A549 cells derived from lung. Phenanthroline protected cells from toxicity of phenanthraquinone.2.Cytotoxicity of arsenic compoundsArsenic activates transcription factor Nrf2 and activate expression of genes such as HO-1,Prx I and A170, the protein accumulated as ubiquitin-conjugated form. Sulforaphane, Nrf2 activating natural compounds, had a beneficial effects against arsenic toxicity.3.Analysis of model mice in lifestyle-related illnessesWe constructed Prx I-deficient transgenic mice. The mutant mice showed higher sensitivity of tissue oxidative damage to Fe-NTA. The mice showed lower capacity to remove nitroxyl radicals. We also constructed A170-deficient mice. These mice show overeating and obesity, causing insulin-resistance.