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Title: Mechanism of toxicity of hydrogen peroxide

Thesis/Dissertation ·
OSTI ID:5559874

We examined the capacity of hydrogen peroxide to injure E. coli. Externally applied hydrogen peroxide rapidly permeates the bacterial cell and causes at least two classes of potentially lethal damage. These classes were initially distinguished by the kinetics of their production. Additional distinctions have been made regarding the chemistry of cell injury and the details of the cell response. One class of cell damage consists of DNA lesions; if unrepaired, mode one killing results. Hydrogen peroxide does not directly attack the DNA. Instead, ferrous iron reduces the peroxide to generate a hydroxyl-radical-like species, which acts as a DNA oxidant. The peculiar kinetics of mode-one killing may reflect an high reaction rate between this radical and peroxide itself. Interestingly, NADH may chemically reduce ferric iron in order to start and maintain the sequence of redox reactions. The target of the other class of cell damage is unknown. This damage, unlike that associated with mode-one killing, does not rely upon Fenton chemistry. Scavenging enzymes, such as catalase and superoxide dismutase, contribute to resisting oxidative stress. Increases in catalase titer accelerate detoxification of peroxide and are responsible for the protective effects of oxyR induction. When oxidants elude this defense and nick DNA, a variety of enzymes-exonuclease III, endonuclease IV, and DNA polymerase I-repair the damage.

Research Organization:
California Univ., Berkeley, CA (USA)
OSTI ID:
5559874
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English