DNA damage by bromate: mechanism and consequences.
Exposure of mammalian cells to bromate (BrO3-) generates oxidative DNA modifications, in particular 7,8-dihydro-8-oxo-guanine (8-oxoG). The damaging mechanism is quite unique, since glutathione, which is protective against most oxidants and alkylating agents, mediates a metabolic activation, while bromate itself does not react directly with DNA. Neither enzymes nor transition metals are required as catalysts in the activation. The ultimate DNA damaging species has not yet been established, but experiments under cell-free conditions suggest that neither molecular bromine nor reactive oxygen species such as superoxide, hydrogen peroxide or singlet oxygen are involved. Rather bromine radicals (Br*) or oxides (BrO*, BrO2*) might be responsible. Compared to hypochlorite (ClO-), bromate is much less cytotoxic, probably because the former halite efficiently reacts with proteins and other vitally important cellular constituents. In consequence, oxidative DNA damage and the induction of mutations and micronuclei is easily detectable at non-cytotoxic concentrations of bromate, while DNA damage by hypochlorite is observed only at cytotoxic concentrations and follows a non-linear (hockey-stick-like) dose response.
Institute of Pharmacy, University of Mainz, D-55099 Mainz, Germany.
Daniel
D
Ballmaier
Bernd
B
Epe
D000818:Animals; D001959:Bromates / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
C453560:7,8-dihydro-8-oxoguanine; D001959:Bromates; D009153:Mutagens; D017382:Reactive Oxygen Species; C019536:potassium bromate; D006147:Guanine