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

Li MJ, Wang WW, Chen SW, Shen Q, Min R - Med. Sci. Monit. (2011)

Bottom Line: The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation Medicine, Department of Naval Medicine, 2nd Military Medical University, Shanghai, China.

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.

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Related in: MedlinePlus

Temporal responses of CDKN1A (A) and ATM (B) gene expression at different exposure doses are plotted. Points denote the mean of responses in 5 different mice; error bars denote SD.
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f1-medscimonit-17-10-br290: Temporal responses of CDKN1A (A) and ATM (B) gene expression at different exposure doses are plotted. Points denote the mean of responses in 5 different mice; error bars denote SD.

Mentions: CDKN1A, which has a regulatory role in S phase DNA replication and is known to be activated by the tumor protein p53 (TP 53), had the strongest upregulation in expression level out of the 11 genes investigated in this study. As shown in Figure 1A, compared with the non-irradiated control, CDKN1A gene expression gradually increased to a maximum value of approximately 88-fold for 2 Gy (p<0.0001) and 130-fold for 4 Gy (p<0.0001) at 12 h post-irradiation, and approximately 116-fold for 6 Gy (p<0.0001) and 100-fold for 8 Gy (p<0.0001) at 8 h post-exposure. Then, CDKN1A gene expression gradually decreased but remained greater than 30-fold (p<0.05) higher than that of the control group at 48 h post-irradiation for all exposure doses. Figure 2A and B show the significant differences in CDKN1A gene expression induced by the different exposure doses. Significant differences can be seen by comparing the exposure groups of 2 and 6 Gy (p<0.05), 4 and 6 Gy (p<0.0001), and 4 and 8 Gy (p<0.001) at 8 h post-exposure (Figure 2A). At the 12 h post-irradiation time point, CDKN1A gene expression decreased along with an increase in exposure dose. The only significant difference was between 2 and 8 Gy.


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

Li MJ, Wang WW, Chen SW, Shen Q, Min R - Med. Sci. Monit. (2011)

Temporal responses of CDKN1A (A) and ATM (B) gene expression at different exposure doses are plotted. Points denote the mean of responses in 5 different mice; error bars denote SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539470&req=5

f1-medscimonit-17-10-br290: Temporal responses of CDKN1A (A) and ATM (B) gene expression at different exposure doses are plotted. Points denote the mean of responses in 5 different mice; error bars denote SD.
Mentions: CDKN1A, which has a regulatory role in S phase DNA replication and is known to be activated by the tumor protein p53 (TP 53), had the strongest upregulation in expression level out of the 11 genes investigated in this study. As shown in Figure 1A, compared with the non-irradiated control, CDKN1A gene expression gradually increased to a maximum value of approximately 88-fold for 2 Gy (p<0.0001) and 130-fold for 4 Gy (p<0.0001) at 12 h post-irradiation, and approximately 116-fold for 6 Gy (p<0.0001) and 100-fold for 8 Gy (p<0.0001) at 8 h post-exposure. Then, CDKN1A gene expression gradually decreased but remained greater than 30-fold (p<0.05) higher than that of the control group at 48 h post-irradiation for all exposure doses. Figure 2A and B show the significant differences in CDKN1A gene expression induced by the different exposure doses. Significant differences can be seen by comparing the exposure groups of 2 and 6 Gy (p<0.05), 4 and 6 Gy (p<0.0001), and 4 and 8 Gy (p<0.001) at 8 h post-exposure (Figure 2A). At the 12 h post-irradiation time point, CDKN1A gene expression decreased along with an increase in exposure dose. The only significant difference was between 2 and 8 Gy.

Bottom Line: The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Radiation Medicine, Department of Naval Medicine, 2nd Military Medical University, Shanghai, China.

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.

Show MeSH
Related in: MedlinePlus