Up-regulation of 8-oxo-dGTPase activity of MTH1 protein in the brain, testes and kidneys of mice exposed to (137)Cs gamma radiation.

2.50
Hdl Handle:
http://hdl.handle.net/10146/114949
Title:
Up-regulation of 8-oxo-dGTPase activity of MTH1 protein in the brain, testes and kidneys of mice exposed to (137)Cs gamma radiation.
Authors:
Bialkowski, Karol; Szpila, Anna; Kasprzak, Kazimierz S.
Abstract:
Abstract Mammalian MTH1 protein is an antimutagenic (2'-deoxy)ribonucleoside 5'-triphosphate pyrophosphohydrolase that prevents the incorporation of oxidatively modified nucleotides into nucleic acids. It decomposes most specifically the miscoding products of oxidative damage to purine nucleic acid precursors (e.g. 8-oxo-dGTP, 2-oxo-dATP, 2-oxo-ATP, 8-oxo-GTP) that may cause point mutations or transcription errors when incorporated into DNA and RNA, respectively. The increased expression of MTH1 mRNA and MTH1 protein was previously proposed as a molecular marker of oxidative stress. Therefore, we hypothesized that increased 8-oxo-dGTPase activity of MTH1 protein in mouse organs could serve as a dose-dependent marker of exposure to ionizing radiation, which is known to induce oxidative stress. To test our hypothesis, we measured 8-oxo-dGTPase activity in six organs of male BL6 mice after exposure to 0, 10, 25 and 50 cGy and 1 Gy of (137)Cs gamma radiation given as a single whole-body dose (1 Gy/min). The mice were killed 4, 8 and 24 h after irradiation. A statistically significant induction of 8-oxo-dGTPase was found in brains, testes and kidneys but not in lungs, hearts or livers. Brains, which demonstrated the highest (4.3-fold) increase of 8-oxo-dGTPase activity, were shown to express approximately 50% higher levels of MTH1 protein. However, due to the lack of a simple positive correlation between the dose and the observed 8-oxo-dGTPase activity in brain, testes and kidneys, we conclude that measurements of 8-oxo-dGTPase activity in these organs may serve as a rough indicator rather than a quantifiable marker of radiation-induced oxidative stress.
Citation:
Radiat. Res. 2009, 172 (2):187-197
Journal:
Radiation Research
Issue Date:
Aug-2009
URI:
http://hdl.handle.net/10146/114949
DOI:
10.1667/RR1636.1
PubMed ID:
19630523
Type:
Article
Language:
en
ISSN:
0033-7587
Sponsors:
This research was supported by grants 41/6.PR UE/2007/7 and 3P04A 06323 from the Polish State Committee for Scientific Research and the Intramural Research Program of the U.S. NIH, National Cancer Institute, Center for Cancer Research. KB and AS are partners of ECNIS (European Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (Contract No 513943). The authors are thankful to Dr. Gary Pauly for his insightful critical comments on this manuscript. KB has dedicated this work to the memory of Marek Grechuta.
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DC FieldValue Language
dc.contributor.authorBialkowski, Karolen
dc.contributor.authorSzpila, Annaen
dc.contributor.authorKasprzak, Kazimierz S.en
dc.date.accessioned2010-11-08T12:25:02Z-
dc.date.available2010-11-08T12:25:02Z-
dc.date.issued2009-08-
dc.identifier.citationRadiat. Res. 2009, 172 (2):187-197en
dc.identifier.issn0033-7587-
dc.identifier.pmid19630523-
dc.identifier.doi10.1667/RR1636.1-
dc.identifier.urihttp://hdl.handle.net/10146/114949-
dc.description.abstractAbstract Mammalian MTH1 protein is an antimutagenic (2'-deoxy)ribonucleoside 5'-triphosphate pyrophosphohydrolase that prevents the incorporation of oxidatively modified nucleotides into nucleic acids. It decomposes most specifically the miscoding products of oxidative damage to purine nucleic acid precursors (e.g. 8-oxo-dGTP, 2-oxo-dATP, 2-oxo-ATP, 8-oxo-GTP) that may cause point mutations or transcription errors when incorporated into DNA and RNA, respectively. The increased expression of MTH1 mRNA and MTH1 protein was previously proposed as a molecular marker of oxidative stress. Therefore, we hypothesized that increased 8-oxo-dGTPase activity of MTH1 protein in mouse organs could serve as a dose-dependent marker of exposure to ionizing radiation, which is known to induce oxidative stress. To test our hypothesis, we measured 8-oxo-dGTPase activity in six organs of male BL6 mice after exposure to 0, 10, 25 and 50 cGy and 1 Gy of (137)Cs gamma radiation given as a single whole-body dose (1 Gy/min). The mice were killed 4, 8 and 24 h after irradiation. A statistically significant induction of 8-oxo-dGTPase was found in brains, testes and kidneys but not in lungs, hearts or livers. Brains, which demonstrated the highest (4.3-fold) increase of 8-oxo-dGTPase activity, were shown to express approximately 50% higher levels of MTH1 protein. However, due to the lack of a simple positive correlation between the dose and the observed 8-oxo-dGTPase activity in brain, testes and kidneys, we conclude that measurements of 8-oxo-dGTPase activity in these organs may serve as a rough indicator rather than a quantifiable marker of radiation-induced oxidative stress.en
dc.description.sponsorshipThis research was supported by grants 41/6.PR UE/2007/7 and 3P04A 06323 from the Polish State Committee for Scientific Research and the Intramural Research Program of the U.S. NIH, National Cancer Institute, Center for Cancer Research. KB and AS are partners of ECNIS (European Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (Contract No 513943). The authors are thankful to Dr. Gary Pauly for his insightful critical comments on this manuscript. KB has dedicated this work to the memory of Marek Grechuta.en
dc.language.isoenen
dc.subjectGamma Raysen
dc.subjectCesium Radioisotopesen
dc.subjectWhole-Body Irradiationen
dc.subjectBrainen
dc.subjectKidneyen
dc.subjectTestisen
dc.subjectEnzyme Activationen
dc.subjectDNA Repair Enzymesen
dc.subjectGene Expression Regulationen
dc.subjectAnimalsen
dc.subject.meshAnimals-
dc.subject.meshBrain-
dc.subject.meshCesium Radioisotopes-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshEnzyme Activation-
dc.subject.meshGamma Rays-
dc.subject.meshGene Expression Regulation, Enzymologic-
dc.subject.meshHeavy Ions-
dc.subject.meshKidney-
dc.subject.meshMale-
dc.subject.meshMetabolic Clearance Rate-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshOrgan Specificity-
dc.subject.meshPhosphoric Monoester Hydrolases-
dc.subject.meshTestis-
dc.subject.meshTissue Distribution-
dc.subject.meshUp-Regulation-
dc.subject.meshWhole-Body Irradiation-
dc.titleUp-regulation of 8-oxo-dGTPase activity of MTH1 protein in the brain, testes and kidneys of mice exposed to (137)Cs gamma radiation.en
dc.typeArticleen
dc.identifier.journalRadiation Researchen
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