In vivo DNA adduct formation by bisphenol A

Environ Mol Mutagen. 1995;26(1):60-6. doi: 10.1002/em.2850260109.


We have previously shown that bisphenol A (BPA) is oxidized to bisphenol-o-quinone in the presence of activation system and that the chemical reaction of DNA or deoxyguanosine 3'-monophosphate (dGMP) with bisphenol-o-quinone produces adducts. In the present study, using the 32P-postlabeling technique, we have investigated the in vivo DNA adduct formation by BPA by examining covalent modification in DNA. Administration of a single or multiple dose of 200 mg/kg of BPA to CD1 male rats produced two major and several minor adducts in liver DNA. The two major in vivo adducts matched the adduct profile of DNA or dGMP-bisphenol-o-quinone. To determine how BPA may be converted to DNA-binding metabolites, adducts were examined after incubation of DNA with BPA in the presence of a microsomal activation system. The in vitro incubation of BPA with DNA in the presence of a microsomal activation system revealed one major adduct and several minor adducts. The formation of adducts in DNA by BPA in the presence of a microsomal activation system was drastically decreased by known inhibitors of cytochrome P450. Adduct formation in DNA when cumene hydroperoxide or NADPH was used as a cofactor showed adducts with similar chromatographic mobilities as those from the reaction of dGMP-bisphenol-o-quinone. These data demonstrate that BPA is capable of binding covalently to DNA. DNA binding can be inhibited by the inhibitors of cytochrome P450. One of the DNA-binding metabolite(s) both in vitro and in vivo may be bisphenol-o-quinone. Covalent modifications in DNA by in vivo exposure of BPA may be a factor in the induction of hepatotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Biotransformation
  • DNA / chemistry
  • DNA / metabolism
  • DNA Adducts / chemistry
  • DNA Adducts / isolation & purification
  • DNA Adducts / metabolism*
  • Deoxyguanine Nucleotides / chemistry
  • Drug Stability
  • Isotope Labeling / methods
  • Male
  • Microsomes, Liver / metabolism*
  • Mutagens / metabolism
  • Phenols / chemistry
  • Phenols / metabolism*
  • Phosphorus Radioisotopes
  • Rats


  • Benzhydryl Compounds
  • DNA Adducts
  • Deoxyguanine Nucleotides
  • Mutagens
  • Phenols
  • Phosphorus Radioisotopes
  • 2'-deoxyguanosine 5'-phosphate
  • DNA
  • bisphenol A