UVB-exposed chlorinated bisphenol A generates phosphorylated histone H2AX in human skin cells
UVB-exposed chlorinated bisphenol A generates phosphorylated histone H2AX in human skin cells
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DOI：
10.1021/tx800129n
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发表时间：
2008-09-01
影响因子：
4.1
通讯作者：
Toyooka, Tatsushi
中科院分区：
文献类型：
--
作者：
Ibuki, Yuko;Tani, Yukinori;Toyooka, Tatsushi
从废纸回收厂废水中检测出双酚A（BPA）和氯代双酚A（CIBPAs）。先前，我们表明暴露于UV增强了CIBPA的毒性[Mutou（2006）Environ.毒理学. Pharmacol. 21，283-289和Mutou（2008）Toxicol. in Vitro 22，864-872）。BPA和CIBPAs在环境中暴露于阳光下，然而，关于其光降解过程中毒性变化的研究很少，特别是CIBPAs。在这项使用人角质形成细胞和皮肤成纤维细胞的研究中，我们发现暴露于UVB的3，3 '-二氯双酚A（3，3'-diClBPA）诱导组蛋白H2 AX的磷酸化，该事件被认为是DNA双链断裂形成的标志。用UVB暴露的3，3 '-diClBPA处理的细胞在细胞核中形成磷酸化的历史H2 AX的清晰病灶。即使暴露于高剂量的UVB（类似于200 J/cm 2），未氯化的BPA也不会引起组蛋白H2 AX磷酸化。HPLC分析澄清了具有增加的亲水性的几种化合物通过UVB照射从3，3 '-diCIBPA产生，而不是从BPA产生，表明氯化的化学结构对于与组蛋白H2 AX的磷酸化相关的产物的降解和产生是重要的。在暴露于UVB的3，3 '-diCIBPA的分离峰中，3-羟基双酚A（3-OHBPA）的峰波动与磷酸化组蛋白H2 AX的UVB剂量依赖性外观一致。我们推测UVB照射产生的3-OHBPA参与了BPA的磷酸化过程。考虑到组蛋白H2 AX的磷酸化是维持基因组稳定性和DNA修复所必需的，关注氯化化合物的光产物对于化学品的风险评估非常重要。
Bisphenol A (BPA) and chlorinated bisphenol A (CIBPAs) were detected in wastewater from waste paper recycling plants. Previously, we showed that exposure to UV augmented the toxicity of CIBPAs [Mutou (2006) Environ. Toxicol. Pharmacol. 21, 283-289 and Mutou (2008) Toxicol. in Vitro 22, 864-872). BPA and CIBPAs are exposed to sunlight in the environment; however, research concerning the change of toxicity during their photodegradation is scarce, especially for CIBPAs. 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 historic H2AX in the nucleus. Unchlorinated BPA caused no phosphorylation of histone H2AX even when exposed to high doses of UVB (similar to 200J/cm(2)). HPLC analysis clarified that several compounds with increased hydrophilicity were produced from 3,3'-diCIBPA 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'-diCIBPA 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.