Four halobenzoquinones (HBQs), 2,6-dichloro-1,4-benzoquinone (
DCBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (DCMBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), and
2,6-dibromobenzoquinone (DBBQ), have been recently confirmed as disinfection byproducts (
DBPs) in
drinking water; however, their toxicological information is scarce. Here, we report that HBQs are cytotoxic to T24
bladder cancer cells and that the IC50 values are 95 μM for
DCBQ, 110 μM for DCMBQ, 151 μM for TCBQ, and 142 μM for DBBQ, after a 24-h exposure. The
antioxidant N-acetyl-l-cysteine (NAC) significantly reduces the cytotoxicity induced by the four HBQs, supporting the hypothesis that oxidative stress contributes to the cytotoxicity of HBQs. To further explore the oxidative mechanisms of cytotoxicity, we examined HBQ-induced production of
reactive oxygen species (ROS) in T24 cells, and measured
8-hydroxydeoxyguanosine (8-OHdG),
protein carbonyls, and
malondialdehyde (MDA) adducts of
proteins, markers of oxidative damage to
DNA,
proteins, and
lipids, respectively. All four HBQs generated intracellular ROS in T24 cells in a concentration-dependent manner. HBQs also produced 8-OHdG in genomic
DNA of T24 cells, with the highest levels of 8-OHdG induced by DCMBQ. Protein carbonylation was significantly increased in T24 cells that were incubated with each of the four HBQs for 24 h. However, MDA adduct formation, a marker of lipid peroxidation, was not affected by any of the four HBQs tested. These results suggest that the ROS-induced oxidative damage to
DNA and protein carbonylation are involved in the observed toxicity of HBQs in T24 cells.