title: UVB-exposed chlorinated bisphenol A generates phosphorylated histone H2AX in human skin cells.
abstract: Bisphenol A (BPA) and chlorinated bisphenol A (ClBPAs) were detected in wastewater from waste paper recycling plants. Previously, we showed that exposure to UV augmented the toxicity of ClBPAs [Mutou (2006) Environ. Toxicol. Pharmacol. 21, 283- 289 and Mutou (2008) Toxicol. in Vitro 22, 864- 872]. BPA and ClBPAs are exposed to sunlight in the environment; however, research concerning the change of toxicity during their photodegradation is scarce, especially for ClBPAs. In this study using human keratinocytes and skin fibroblasts, we found that 3,3'-dichlorobisphenol A (3,3'-diClBPA) exposed to UVB induces phosphorylation of histone H2AX, the event considered to be a marker of formation of DNA double strand breaks. The cells treated with the UVB-exposed 3,3'-diClBPA formed clear foci of phosphorylated histone H2AX in the nucleus. Unchlorinated BPA caused no phosphorylation of histone H2AX even when exposed to high doses of UVB (approximately 200 J/cm(2)). HPLC analysis clarified that several compounds with increased hydrophilicity were produced from 3,3'-diClBPA by UVB irradiation, not from BPA, suggesting the chlorinated chemical structure to be important for the degradation and generation of products related to the phosphorylation of histone H2AX. In separated peaks of 3,3'-diClBPA exposed to UVB, peak fluctuation of 3-hydroxybisphenol A (3-OHBPA) was consistent with the UVB dose-dependent appearance of phosphorylated histone H2AX. We suspected that some oxidized BPA involving 3-OHBPA produced by UVB irradiation contributed to the phosphorylation. Considering that the phosphorylation of histone H2AX is required for maintaining the genome's stability and the repair of DNA, attention to photoproducts from chlorinated compounds is important for the risk evaluation of chemicals.
authors: Laboratory of Radiation Biology, Graduate School of Nutritional and Environmental Sciences, Institute for Environmental Sciences, University of Shizuoka, Shizuoka-shi 422-8526, Japan ibuki@u-shizuoka-ken.ac.jp
authors: Yuko
authors: Y
authors: Ibuki
authors: Yukinori
authors: Y
authors: Tani
authors: Tatsushi
authors: T
authors: Toyooka
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D010766:Phosphorylation / Q000187:drug effects; D012867:Skin / Q000166:cytology*; D013194:Staining and Labeling; D014466:Ultraviolet Rays; D000098826:Bisphenol A Compounds
chemical_list: D006657:Histones; D010636:Phenols; C534679:3,3'-dichlorobisphenol A; D000098826:Bisphenol A Compounds; C468783:H2AX protein, human