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01 October 2011

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells

Ming-juan LiBCDEF, Wei-wei WangBC, Shi-wei ChenBC, Qian ShenD, Rui MinADFG

DOI: 10.12659/MSM.881976

Med Sci Monit 2011; 17(10): BR290-297

Abstract

Background: The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles.
Material/Methods: Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0–8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR).
Results: Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2–8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges.
Conclusions: The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

Keywords: Mice, Inbred BALB C, Leukocytes - radiation effects, Gene Expression Regulation - radiation effects, Gamma Rays, Dose-Response Relationship, Radiation, DNA-Binding Proteins - metabolism, DNA Repair - genetics, Cyclin-Dependent Kinase Inhibitor p21 - metabolism, Cobalt Radioisotopes - administration & dosage, Cell Cycle Proteins - metabolism, Ataxia Telangiectasia Mutated Proteins, Protein-Serine-Threonine Kinases - metabolism, Radiometry - methods, Real-Time Polymerase Chain Reaction, Tumor Suppressor Proteins - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750