In vitro conversion of environmental estrogenic chemical bisphenol A to DNA binding metabolite(s).
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.
Atkinson
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A
Department of Environmental Health Sciences, University of Alabama, Birmingham 35294-0008, USA.
Roy
D
D
D001559:Benzhydryl Compounds; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004789:Enzyme Activation; D004967:Estrogens / Q000378:metabolism; D006900:Hydroxylation; D010544:Peroxidases / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D013057:Spectrum Analysis; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004247:DNA; D018736:DNA Adducts; D004967:Estrogens; D010544:Peroxidases; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds