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Citations to this article

Damage to the bases in DNA induced by stimulated human neutrophils.
J H Jackson, … , C G Cochrane, M Dizdaroglu
J H Jackson, … , C G Cochrane, M Dizdaroglu
Published November 1, 1989
Citation Information: J Clin Invest. 1989;84(5):1644-1649. https://doi.org/10.1172/JCI114342.
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Research Article

Damage to the bases in DNA induced by stimulated human neutrophils.

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Abstract

Leukocyte-induced DNA damage may partially account for the known association between chronic inflammation and malignancy. Since elucidation of the chemical nature of leukocyte-induced DNA damage may enhance our understanding of the mechanisms underlying leukocyte-induced DNA damage and the carcinogenesis associated with inflammation, the present study was undertaken to characterize the chemical modifications that occur in DNA exposed to stimulated human neutrophils. Calf thymus DNA was exposed to phorbol myristate acetate (PMA)-stimulated neutrophils in the presence or absence of exogenously added iron ions. DNA samples were subsequently hydrolyzed, derivatized and analyzed by gas chromatography-mass spectrometry with selected-ion monitoring. A variety of base modifications including cytosine glycol, thymine glycol, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine were identified. The yield of these various base products was increased by the addition of iron ions. Specifically, in the presence of physiologic quantities of iron ions, approximately 7 of every 1,000 DNA bases were modified. Addition of the superoxide anion scavenger, superoxide dismutase, the hydrogen peroxide scavenger, catalase, the hydroxyl scavenger, dimethylsulfoxide, or the iron chelator, deferoxamine, to DNA mixtures containing PMA, neutrophils, and iron ions, greatly decreased the yield of the damaged DNA base products. Our results indicate that stimulated human neutrophils can damage each of the four bases in DNA. It is likely that hydroxyl radical, generated via an iron catalyzed Haber-Weiss reaction, mediates neutrophil-induced DNA base damage, since: (a) the chemical structure of neutrophil-induced DNA base damage is consistent with a hydroxyl radical-mediated mechanism, (b) hydroxyl radical generated via ionizing radiation in aqueous solution produces DNA base modifications that are identical to neutrophil-induced DNA base modifications, (c) iron ions increase neutrophil-induced DNA base damage, and (d) iron chelators or scavengers of superoxide anion, hydrogen peroxide or hydroxyl radical decrease neutrophil-induced DNA base damage.

Authors

J H Jackson, E Gajewski, I U Schraufstatter, P A Hyslop, A F Fuciarelli, C G Cochrane, M Dizdaroglu

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Total citations by year

Year: 2023 2020 2016 2015 2013 2012 2010 2009 2007 2006 2005 2004 2002 2001 2000 1999 1997 1996 1995 1994 1993 1992 1991 1990 1984 1983 Total
Citations: 1 3 1 2 1 1 4 1 5 3 2 2 3 4 2 4 7 5 6 7 7 9 15 1 1 1 98
Citation information
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Citations to this article in year 2020 (3)

Title and authors Publication Year
Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast
JS Helm, RA Rudel
Archives of Toxicology 2020
Role of the Neutrophil in the Pathogenesis of Advanced Cancer and Impaired Responsiveness to Therapy
BL Rapoport, HC Steel, AJ Theron, T Smit, R Anderson
Molecules (Basel, Switzerland) 2020
Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part II: Relation between ROS-induced DNA damages and human cancer
R Nilsson, NA Liu
2020

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