Atkinson A, Roy D
Department of Environmental Health Sciences, University of Alabama, Birmingham 35294-0008, USA.
Biochem Biophys Res Commun. 1995 May 16;210(2):424-33. doi: 10.1006/bbrc.1995.1678.
In the present study we have investigated the ability of bisphenol A to be converted to reactive metabolite(s) and its potential to bind to DNA. In this in vitro study we show that bisphenol A is oxidized by 70% to bisphenol o-quinone. The evidence for the formation of bisphenol o-quinone was shown by UV, IR and GC-MS. The new product, bisphenol o-quinone, had a maximum UV absorption at 386 nM, the appearance of an IR characteristic of unsaturated carbonyl (1690 cm-1) and a mass of 242. The chemical reaction of deoxyguanosine monophosphate (dGMP) or DNA with bisphenol o-quinone produced 6-8 adducts. The in vitro incubation of DNA with bisphenol A in the presence of peroxidase activation system also produced one major and seven minor adducts. The chromatographic mobilities of major DNA adducts four and six formed by bisphenol A in the presence of peroxidase activation system closely matched those of spots four and six obtained by chemical reaction between DNA or dGMP with bisphenol o-quinone. Based on these data it appears that bisphenol A is converted to DNA binding metabolites in vitro. Whether irreversible binding of bisphenol A to DNA through metabolic activation may be responsible for some of the toxic effects produced by bisphenol A is not clear.
在本研究中，我们调查了双酚A转化为活性代谢物的能力及其与DNA结合的潜力。在这项体外研究中，我们表明双酚A有70%被氧化为双酚邻醌。通过紫外光谱（UV）、红外光谱（IR）和气相色谱 - 质谱联用（GC - MS）证明了双酚邻醌的形成。新产物双酚邻醌在386 nM处有最大紫外吸收，出现了不饱和羰基的红外特征峰（1690 cm-1），分子量为242。脱氧鸟苷单磷酸（dGMP）或DNA与双酚邻醌的化学反应产生了6 - 8种加合物。在过氧化物酶激活系统存在的情况下，DNA与双酚A的体外孵育也产生了一种主要加合物和七种次要加合物。在过氧化物酶激活系统存在下，双酚A形成的主要DNA加合物4和6的色谱迁移率与DNA或dGMP与双酚邻醌化学反应得到的斑点4和6的色谱迁移率紧密匹配。基于这些数据，似乎双酚A在体外可转化为与DNA结合的代谢物。双酚A通过代谢激活与DNA的不可逆结合是否可能是其产生某些毒性作用的原因尚不清楚。
