6533b872fe1ef96bd12d42f0

RESEARCH PRODUCT

DNA damage by bromate: Mechanism and consequences

Daniel BallmaierBernd Epe

subject

GuanineCell SurvivalDNA damageHypochloriteToxicologymedicine.disease_causeMicechemistry.chemical_compoundCricetulusCell Line TumorCricetinaemedicineAnimalsHydrogen peroxideMicronuclei Chromosome-Defectivechemistry.chemical_classificationReactive oxygen speciesMicronucleus TestsDose-Response Relationship DrugBromatesSinglet oxygenSuperoxideBromatechemistryBiochemistryReactive Oxygen SpeciesOxidative stressDNA DamageMutagens

description

Abstract 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.

yearjournalcountryeditionlanguage
2005-09-08Toxicology
https://doi.org/10.1016/j.tox.2006.01.009