New Evidence for Toxicity of Polybrominated Diphenyl Ethers: DNA Adduct Formation from Quinone Metabolites

摘要

This study investigated the formation of DNA adducts of polybrominated diphenyl ethers (PBDEs) and the possible mechanisms. DNA adduction was conducted by in vitro reaction of deoxyguanosine (dG) and DNA with PBDE-quinone (PBDE-Q) metabolites, and DNA adducts were characterized by using electrospray ionization tandem mass spectro-metry. The results suggested DNA adduction involved Michael Addition between the exocydic NH2 group at the N-2 position of dG and the electron-deficient carbon of quinone, followed by reductive cydization with loss of (bromo-)l-hydroperoxy-ben-zene or water to form a type I or type II adduct PBDE-Qwith substituted bromine on the quinone ring was proven to be a favorable structure to form a type I adduct, while the absence of bromine on the quinone ring resulted in a type II adduct. Lower reactivity of adduction was also observed with increasing the number of bromine atoms on the phenoxyl ring. Our data clearly demonstrated PBDEs could covakntly bind to DNA mediated by quinone metabolites, depending on the degree of bromine substitution. This study opened a new view on the mechanism of toxicity of PBDEs and reported the structure of PBDE-DNA adducts, which might be valuable for the evaluation on potential in vivo formation of PBDE-DNA adducts.