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Research Article Free access | 10.1172/JCI113660

Oxidant-induced DNA damage of target cells.

I Schraufstätter, P A Hyslop, J H Jackson, and C G Cochrane

Department of Immunology, Scripps Clinic, La Jolla, California 92037.

Find articles by Schraufstätter, I. in: JCI | PubMed | Google Scholar

Department of Immunology, Scripps Clinic, La Jolla, California 92037.

Find articles by Hyslop, P. in: JCI | PubMed | Google Scholar

Department of Immunology, Scripps Clinic, La Jolla, California 92037.

Find articles by Jackson, J. in: JCI | PubMed | Google Scholar

Department of Immunology, Scripps Clinic, La Jolla, California 92037.

Find articles by Cochrane, C. in: JCI | PubMed | Google Scholar

Published September 1, 1988 - More info

Published in Volume 82, Issue 3 on September 1, 1988
J Clin Invest. 1988;82(3):1040–1050. https://doi.org/10.1172/JCI113660.
© 1988 The American Society for Clinical Investigation
Published September 1, 1988 - Version history
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Abstract

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks.

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