Bactericidal potency of hydroxyl radical in physiological environments.
Rates of radiolytic inactivation of bacteria suspended in N2O-saturated solutions were dramatically increased over normal background levels when the media contained chloride or bicarbonate ions. The bacteria could be protected from this enhanced toxicity by the addition of free radical scavengers (ethanol, ascorbate, hydrogen peroxide, mannitol, glucose, EDTA, picolinic acid), indicating that the lethal reactions were extracellular in origin. Prior irradiation of chloride-containing solutions led to formation of hypochlorous acid, which was identified by detection of ring-chlorinated products when reacted with fluorescein. Prolonged irradiation of other solutions did not lead to accumulation of bactericidal agents; however, irradiation of bicarbonate-containing solutions in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) led to formation of the EPR-detectable DMPO.CO3- adduct. The results are interpreted in terms of formation of secondary radicals, among which the carbonate and chlorine radicals are uniquely toxic to bacteria. From rate comparisons of the solution components, it was concluded that the reactions involving chloride ion are unlikely to be expressed in biological environments, but that the CO3- radical could be an important intermediary oxidant in peroxide-inflicted cellular damage, particularly in spatially confined environments such as the leukocyte phagosome.
Wolcott
R G
RG
Department of Chemistry, Biochemistry, and Molecular Biology, Oregon Graduate Institute of Science and Technology, Portland 97291-1000.
Franks
B S
BS
Hannum
D M
DM
Hurst
J K
JK
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects; D000431:Ethanol / Q000494:pharmacology; D016166:Free Radical Scavengers; D005720:Gamma Rays; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000633:toxicity*; D007700:Kinetics; D013294:Lactococcus lactis / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects; D008027:Light; D008353:Mannitol / Q000494:pharmacology; D008954:Models, Biological; D010848:Picolinic Acids / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects
D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D010848:Picolinic Acids; D017665:Hydroxyl Radical; D000431:Ethanol; D008353:Mannitol; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D005947:Glucose; D001205:Ascorbic Acid; C030614:picolinic acid