Study of multiple effects between air pollutions and ultraviolet A

在这项研究中，我们探讨了多环芳烃（PAHs）和紫外线A（UVA）共同暴露后的免疫抑制机制。苯并[a]芘（Benzo[a]pyrene，BaP）是多环芳烃（PAHs）中研究最多的一种。用脉冲场凝胶电泳和DNA双链断裂修复酶缺陷细胞系证实了BaP和UVA共暴露可引起DNA双链断裂。此外，已经证实在暴露于电离辐射和抗肿瘤剂等之后在DSB位点产生的组蛋白H2 AX（γ-H2 AX）的磷酸化，BaP和UVA联合暴露后，BAP的表达显著增加。γ-H_2AX在低剂量的BaP和UVA下可被检测到，而UVA对γ-H_2AX无细胞毒性。因此，γ-H2 AX的检测被认为是有用的灵敏检测的光毒性的环境化学品。此外，DSB的修复与γ-H2 AX有关，提示γ-H2 AX在多环芳烃和UVA共同暴露后是抑制皮肤癌发生的重要过程。我们正在计划构建新的评价系统，重点是其他组蛋白修饰。此外，γ-H2 AX与多环芳烃和UVA共同暴露后免疫系统抑制的关系有待进一步研究。

In this study, we examined the mechanism of immune suppression after coexposure to polycyclic aromatic hydrocarbons (PAHs) and ultraviolet A (UVA). As the high cytotoxicity was considered one of the reasons for immune suppression after coexposure, we focused on clarification of the mechanism of cytotoxicity.Benzo[a]pyrene (BaP) is one of the most commonly studied PAHs. Coexposure to BaP and UVA induced DNA double strand breaks (DSBs), which was confirmed by pulse-field gel electrophoresis and using DSBs repair enzyme-deficient cell line. Furthermore, phosphorylation of histone H2AX (γ-H2AX) which has been clarified to be generated at the sites of DSBs after exposure to ionizing radiation and antitumor agents, etc., was significantly increased after coexposure to BaP and UVA. γ-H2AX was detectable at low doses of BaP and UVA which had no cytotoxicity. Therefore, the detection of γ-H2AX is considered to be useful for sensitive detection of phototoxicty of environmental chemicals. In addition, the repair of DSBs was relative to γ-H2AX, suggesting that γ-H2AX after coexposure to PAHs and UVA was an important process to suppress the promotion of skin cancer.This is the first study to evaluate the effects of environmental chemicals in the point of histone modification change. We are planning to construct new evaluation systems focused on other histone modification. In addition, the relationship between γ-H2AX and suppression of immune system after coexposure to PAHs and UVA is a future subject to be clarified.