Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro.
Exposure of Escherichia coli to low concentrations of hydrogen peroxide results in DNA damage that causes mutagenesis and kills the bacteria, whereas higher concentrations of peroxide reduce the amount of such damage. Earlier studies indicated that the direct DNA oxidant is a derivative of hydrogen peroxide whose formation is dependent on cell metabolism. The generation of this oxidant depends on the availability of both reducing equivalents and an iron species, which together mediate a Fenton reaction in which ferrous iron reduces hydrogen peroxide to a reactive radical. An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide. The direct DNA oxidant both in vivo and in this in vitro system exhibits reactivity unlike that of a free hydroxyl radical and may instead be a ferryl radical.
Imlay
J A
JA
Department of Biochemistry, University of California, Berkeley 94720.
Chin
S M
SM
Linn
S
S
D010582:Bacteriophage lambda; D055598:Chemical Phenomena; D002621:Chemistry; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D005296:Ferrous Compounds; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides; D017665:Hydroxyl Radical; D010084:Oxidation-Reduction
D004269:DNA, Bacterial; D005296:Ferrous Compounds; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide