Up-regulation of 8-oxo-dGTPase Activity of MTH1 Protein in the Brain, Testes and Kidneys of Mice Exposed to137Cs γ Radiation
| Autor: | Kazimierz S. Kasprzak, Anna Szpila, Karol Bialkowski |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Metabolic Clearance Rate DNA repair Biophysics Biology Kidney medicine.disease_cause Gene Expression Regulation Enzymologic Mice chemistry.chemical_compound Transcription (biology) Testis medicine Animals Heavy Ions Tissue Distribution heterocyclic compounds Radiology Nuclear Medicine and imaging Nucleotide chemistry.chemical_classification Messenger RNA Radiation Brain RNA Molecular biology Phosphoric Monoester Hydrolases Up-Regulation Enzyme Activation Mice Inbred C57BL DNA Repair Enzymes Gene Expression Regulation chemistry Biochemistry Gamma Rays Cesium Radioisotopes Organ Specificity Nucleic acid Whole-Body Irradiation DNA Oxidative stress |
| Zdroj: | Radiation Research. 172:187-197 |
| ISSN: | 1938-5404 0033-7587 |
| DOI: | 10.1667/rr1636.1 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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