260 - Mechanism of DNA Double-Strand Cleavage by a New Chlorination Disinfection Byproduct Trichloro-1,4-Benzoquinone and H2O2 and Protection by Thiol-Containing Drugs

Abstract

Trichloro-1,4-benzoquinone (TriCBQ) has been recently identified as a new chlorination disinfection byproduct in drinking water and swimming pool water. We found previously that the highly reactive and biologically important • OH can be produced by halogenated quinones and H 2 O 2 independent of transition metal ions. However, it is not clear whether DNA double-strand breaks (DSBs) can be induced by TriCBQ in the presence of H 2 O 2 ; and if so, whether TriCBQ/H 2 O 2 induced DNA DSBs can be protected by thiol-containing drugs? Here we show that DNA DSBs can be generated only when pBR322 DNA was treated with the combination of both TriCBQ and H 2 O 2 , while either TriCBQ or H 2 O 2 alone cannot. Typical ● OH scavengers such as dimethyl sulfoxide and ethanol can markedly inhibit TriCBQ/H 2 O 2 -induced DSBs, and a good correlation was observed between DNA DSBs and ● OH generation by TriCBQ/H 2 O 2 as measured by ESR spin-trapping method. DNA damage induced by TriCBQ/H 2 O 2 could be inhibited by several thiol-containing drugs such as captopril, penicillamime, N -acetyl-cysteine and 2,3-dimercaptosuccinic acid. The protection was found to be due to their direct interactions with TriCBQ to form the less reactive quinone-thiol conjugates.