Reactivity of bisphenol A-3,4-quinone with DNA. A quantum chemical study

Bisphenol A is a primary component of polycarbonate plastics found in many different products - from reusable drink bottles to cell phones. It is also an important component of epoxy resins, which serve as a protective layer inside food and drink cans. Chronic exposure to bisphenol A from food, drink and other sources is the reason that this chemical shows up at low levels in the urine of nearly everyone. Bisphenol A is a known endocrine disruptor with a variety of other effects, including genotoxicity. These facts have created a lot of concern about how toxic it is. To investigate the possible genotoxic mechanisms of bisphenol A we calculated the chemical reactivity of the bisphenol A metabolite bisphenol A-3,4-quinone with deoxyguanosine by using density functional theory in conjunction with Langevin dipoles solvation model. The calculated activation free energy of 23.1 kcal/mol shows that bisphenol A-3,4-quinone could form an adduct with deoxyguanosine and could be a mutagen. The subsequent depurination reaction was also studied with the same methodology. The calculated activation energy was 22.5 kcal/mol, providing evidence that the rate-limiting step essential to causing genotoxicity is nucleophilic addition of the N7-deoxyguanosine to bisphenol A-3,4-quinone rather than depurination. (C) 2011 Elsevier Ltd. All rights reserved.