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The Nucleotide Pool, a Target for Low-Dose gamma-Ray-Induced Oxidative Stress
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
2008 (English)In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 170, no 6, 776-783 p.Article in journal (Refereed) Published
Abstract [en]

Oxidative stress occurs when the generation of reactive oxygen species (ROS) exceeds the cellular antioxidant capacity. The excess ROS react with and modify cellular components Nucleic acid modifications are of principal interest because they may cause mutations. 8-Oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) is a mutagenic lesion that can be formed by ROS in DNA as well as in the nucleotide pool. 8-Oxo-dG is removed from the DNA by base excision repair and from the nucleotide pool by the nucleotide sanitization enzyme hMTH1. hMTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, which is released to the extracellular environment and can serve as a marker of oxidative stress. The aim of this work was to establish the dose-response relationship for radiation-induced extracellular 8-oxo-dG and hMTH1 in the mGy range of gamma rays in three cellular model systems: human whole blood, human fibroblasts and stimulated lymphocytes. Extracellular 8-oxo-dG was analyzed with the use of an ELISA and hMTH 1 by Western blotting. Our results demonstrate that low-dose ionizing radiation induces a stress response that leads to the formation of extracellular 8-oxo-dG and induction of hMTH 1 in all three cellular model systems tested. This suggests that the nucleotide pool is an important target for radiation-induced stress response.

Place, publisher, year, edition, pages
2008. Vol. 170, no 6, 776-783 p.
Keyword [en]
dna strand breaks; human-cells, mutagenic substrate, chromatin-structure, ionizing-radiation, single-strand, mutt protein, protection, generation, elimination
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-57691ISI: 000261282100009OAI: oai:DiVA.org:su-57691DiVA: diva2:417275
Note
authorCount :2Available from: 2011-05-16 Created: 2011-05-16 Last updated: 2017-12-11Bibliographically approved

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