Ibuki Yuko, Tani Yukinori, Toyooka Tatsushi
Laboratory of Radiation Biology, Graduate School of Nutritional and Environmental Sciences, Institute for Environmental Sciences, University of Shizuoka, Shizuoka-shi 422-8526, Japan
Chem Res Toxicol. 2008 Sep;21(9):1770-6. doi: 10.1021/tx800129n. Epub 2008 Aug 26.
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.
在废纸回收厂的废水中检测到双酚A（BPA）和氯化双酚A（ClBPAs）。此前，我们发现紫外线照射会增强ClBPAs的毒性[Mutou（2006年），《环境毒理学与药理学》21卷，283 - 289页；Mutou（2008年），《体外毒理学》22卷，864 - 872页]。BPA和ClBPAs在环境中会暴露于阳光；然而，关于它们光降解过程中毒性变化的研究很少，尤其是对于ClBPAs。在本研究中，使用人角质形成细胞和皮肤成纤维细胞，我们发现暴露于中波紫外线（UVB）的3,3'-二氯双酚A（3,3'-diClBPA）会诱导组蛋白H2AX磷酸化，该事件被认为是DNA双链断裂形成的标志物。用暴露于UVB的3,3'-diClBPA处理的细胞在细胞核中形成了清晰的磷酸化组蛋白H2AX焦点。未氯化的BPA即使暴露于高剂量的UVB（约200 J/cm²）也不会导致组蛋白H2AX磷酸化。高效液相色谱分析表明，UVB照射使3,3'-diClBPA产生了几种亲水性增加的化合物，而BPA则不会，这表明氯化化学结构对于与组蛋白H2AX磷酸化相关的降解和产物生成很重要。在暴露于UVB的3,3'-diClBPA的分离峰中，3 - 羟基双酚A（3 - OHBPA）的峰波动与磷酸化组蛋白H2AX的UVB剂量依赖性出现一致。我们怀疑UVB照射产生的一些涉及3 - OHBPA的氧化BPA促成了磷酸化。鉴于组蛋白H2AX磷酸化对于维持基因组稳定性和DNA修复是必需的，关注氯化化合物的光产物对于化学品的风险评估很重要。
