The reaction of bisphenol A 3,4-quinone with DNA

Abstract

The 3,4-quinone of the estrogen-active compound bisphenol A (BPA), characterized by a single crystal X-ray structure determination, has been shown by (1)H NMR spectroscopy to react with herring testes DNA, and with deoxyguanosine (dG), in aqueous buffer at pH 7, to form a BPA 3,4-quinone-guanine-N7 adduct (BPAQ-N7-Gua). Presumably this adduct resulted from decomposition (by loss of deoxyribose) of an initially formed, but unstable, BPAQ-N7-dG adduct. Chemical synthesis if BPAQ-N7-Gua, in up to 60% yield, was achieved by the reaction of BPAQ and dG in aqueous acetic acid. Characterization of this product, by NMR spectroscopy and high resolution mass spectrometry, allowed the monitoring (by (1)H NMR spectroscopy) of the reaction of BPAQ with DNA and with dG. The relevance of this adduct formation to the potential mutagenicity and carcinogenicity of BPA will depend upon confirmation of the necessary metabolic oxidative transformation of BPA in vivo.