Interaction of bisphenol A 3,4-quinone metabolite with glutathione and ribonucleosides/deoxyribonucleosides in vitro

•BPAQ was capable of binding directly to the nucleophilic site of ribonucleosides/deoxyribonucleosides in vitro via a Michael addition.•BPAQ produced depurinating adducts that was lost from deoxyribonucleosides, generating apurinic sites in the deoxyribonucleosides.•ESI–MS/MS is a powerful analytical tool for the detection of suspected ribonucleosides/deoxyribonucleosides and GSH adducts. Bisphenol A is a monomer used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners and flame retardants. To determine the genotoxic potential of bisphenol A, the mechanism of the reactions between the reactive electophilic bisphenol A 3,4-quinone (BPAQ) with glutathione and ribonucleosides/deoxyribonucleosides were studied. The obtained results demonstrated that BPAQ reacted with 2′-deoxyguanosine (dG)/guanosine (G), 2′-deoxyadenosine (dA)/adenosine (A), but not with 2′-deoxycytidine (dC)/cytidine (C) and thymidine (T)/uridine (U) in aqueous acetic acid. The reactions were accompanied by loss of deoxyribose, and the rate of depurination by deoxyribonucleoside adducts were faster than that of ribonucleoside adducts. In mixtures of ribonucleosides and deoxyribonucleosides treated with BPAQ, reactions occurred more readily with dG/G than dA/A. The structures of the modified bases were confirmed by electrospray ionization tandem mass spectrometry (ESI–MS/MS). We also found that BPAQ reacted readily with glutathione (GSH) in aqueous acetic acid, and characterized the BPAQ-GSH conjugate by ESI–MS/MS. The in vitro data of depurinating DNA/RNA adducts and BPAQ-GSH adducts may provide appropriate reference for the identification of BPAQ adducts in environmental and biological systems.