Gassman Natalie R, Coskun Erdem, Stefanick Donna F, Horton Julie K, Jaruga Pawel, Dizdaroglu Miral, Wilson Samuel H
Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.
Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States of America; Faculty of Pharmacy, Gazi University, Ankara, Turkey.
PLoS One. 2015 Feb 18;10(2):e0118819. doi: 10.1371/journal.pone.0118819. eCollection 2015.
Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.
双酚A（BPA）是一种具有生物活性的工业化学品，用于生产消费品。由于担心其与肥胖、糖尿病、生殖紊乱和癌症等人类疾病有关联，双酚A已成为公众密切关注的对象。最近的研究将双酚A与活性氧的产生联系起来，而碱基切除修复（BER）负责去除氧化诱导的DNA损伤。然而，双酚A与碱基切除修复之间的关系尚未得到研究。此外，双酚A无处不在的性质使得人类基因组在受到正常的内源性和外源性基因组损伤的同时持续暴露于其环境中，这种共同暴露可能会影响DNA损伤反应和修复。为了确定双酚A暴露对氧化诱导的DNA损伤的碱基切除修复的影响，对双链断裂修复功能受损的细胞单独用双酚A处理，或与溴酸钾（KBrO3）或激光照射作为氧化损伤剂共同暴露。在使用KBrO3的实验中，双酚A与KBrO3共同处理部分逆转了在这些细胞中观察到的KBrO3诱导的细胞毒性，这与基因组DNA中鸟嘌呤碱基损伤的增加同时发生。细胞存活率的提高和氧化诱导的DNA碱基损伤的增加让人想起先前对烷基腺嘌呤DNA糖基化酶缺陷细胞的研究结果，表明双酚A可能会阻止氧化碱基损伤修复的起始。对于激光照射诱导的DNA损伤，双酚A处理抑制了DNA修复，这由几个指标得以揭示。这些结果与双酚A可通过碱基切除修复途径抑制氧化碱基损伤DNA修复的假设一致。
