The multiple influences of glutathione on bromate genotoxicity: implications for the dose-response relationship.
Glutathione displays multiple roles in the oxidative genotoxicity of potassium bromate. On the one hand, reduced glutathione has a demonstrated role in the activation of bromate to species capable of oxidising DNA. However, if this activation should occur within the gut or extracellularly once bromate is absorbed, this may limit the ability of the chemical to oxidise cellular DNA in vivo. Moreover, glutathione may offer protection against the damaging species produced by its interaction with bromate. Finally, if bromate exposure of cells is sufficiently high to deplete glutathione, a secondary oxidative stress and associated DNA damage may occur. These observations would suggest non-linearity in the dose-response to DNA damage in vivo.
Chipman
J K
JK
School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. j.k.Chipman@bham.ac.uk
Parsons
J L
JL
Beddowes
E J
EJ
D000818:Animals; D001959:Bromates / Q000633:toxicity*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*
D001959:Bromates; D009153:Mutagens; D005978:Glutathione