Electrospray ionization tandem mass spectrometric characterization of DNA adducts formed by bromobenzoquinones

Bromobenzoquinones (BBQs) represent a class of reactive metabolites of various aromatic contaminants with bromine-containing substituents, including bromobenzene, bromophenols, polybrominated diphenyl ethers (PBDEs). Recently, 2,6-dibromobenzoquinone also has been detected directly from drinking water. The alternation of the genome caused by covalent binding of chemicals or their metabolites to DNA provides a viable mechanism for carcinogenicity. In the present study, electrospray ionization coupled with ion trap mass spectrometry (ITMS), triple quadrupole MS or quadrupole time-of-flight MS was applied for the analysis of DNA adducts formed by BBQs. The study demonstrated 2-monobromobenzoquinone and 2,6-dibromobenzoquinone could covalently bind to deoxyguanosine (dG) and DNA in vitro. The chemical structures of the DNA adducts were confirmed by accurate mass values, collision-induced fragmentation tandem mass spectra as well as isotopic patterns. Generally, the reaction mechanism for the DNA adduction involved Michael addition between the electron-deficient carbon from the quinone and the nucleophilic exocyclic nitrogen from the dG followed by reductive cyclization with loss of a small molecule such as H(2)O, or HBrO. It was of particular interest to note that some adducts were generated from the reaction of one dG molecule with two BBQ molecules. The obtained results provided new information for assessing the potential cancer risk associated with bromobenzene, bromophenols, PBDEs and BBQs.