In vitro光毒性評価における活性酸素種の影響
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概要
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Three in vitro phototoxicity assays - the photohaemolysis assay, the haemoglobin photo-oxidation assay, and the neutral red uptake assay - were evaluated for use as screening methods in predicting the in vivo phototoxicity of test substances. The photohaemolysis assay evaluates oxygen-dependent membrane damage. The haemoglobin photo-oxidation assay detects haemoglobin oxidation from oxyhaemoglobin to methaemoglobin with UVA irradiation. The neutral red uptake assay evaluates cell survival by assessing the ability of viable cells to take up neutral red dye. Thirty-three test substances were assessed in this study. The phototoxicity predicted in each assay was compared with that in guinea pigs and in human. The phototoxicity predictions made by the in vitro methods were comparatively good. These results suggest that the three in vitro phototoxicity assays could be used to effectively screen chemicals for phototoxicity. The effects of reactive oxygen species in two in vitro phototoxicity methods were assessed. Sixteen test substances that indicated positive reaction in the photohaemolysis assay or the 3T3 neutral red uptake assay were evaluated by using scavengers. Of the 16 test substances, 12 indicated the production of singlet oxygen. Nine of these reacted to histidine used as a scavenger of singlet oxygen. In this study we have confirmed that photodynamic mechanisms play a major role in in vitro phototoxicity reactions. These results suggest that the photohaemolysis assay and the 3T3 neutral red uptake assay could be used to evaluate the photodynamic mechanisms of photosensitizing chemicals. Thus, from the genetic point of view, the production of reactive oxygen species and singlet oxygen responsible for phototoxicity is closely related to the induction of photochemical genotoxicity.
- 日本環境変異原学会の論文
- 2001-10-20