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Combined analysis of gamma-H2AX/53BP1 foci and caspase activation in lymphocyte subsets detects recent and more remote radiation exposures.
- Source :
-
Radiation research [Radiat Res] 2013 Dec; Vol. 180 (6), pp. 603-9. Date of Electronic Publication: 2013 Nov 12. - Publication Year :
- 2013
-
Abstract
- Analysis of gamma-H2AX foci in blood lymphocytes is a promising approach for rapid dose estimation to support patient triage after a radiation accident but has one major drawback: the rapid decline of foci levels post-exposure cause major uncertainties in situations where the exact timing between exposure and blood sampling is unknown. To address this issue, radiation-induced apoptosis (RIA) in lymphocytes was investigated using fluorogenic inhibitors of caspases (FLICA) as an independent biomarker for radiation exposure, which may complement the gamma-H2AX assay. Ex vivo X-irradiated peripheral blood lymphocytes from 17 volunteers showed dose- and time-dependent increases in radiation-induced apoptosis over the first 3 days after exposure, albeit with considerable interindividual variation. Comparison with gamma-H2AX and 53BP1 foci counts suggested an inverse correlation between numbers of residual foci and radiation-induced apoptosis in lymphocytes at 24 h postirradiation (P = 0.007). In T-helper (CD4), T-cytotoxic (CD8) and B-cells (CD19), some significant differences in radiation induced DSBs or apoptosis were observed, however no correlation between foci and apoptosis in lymphocyte subsets was observed at 24 h postirradiation. While gamma-H2AX and 53BP1 foci were rapidly induced and then repaired after exposure, radiation-induced apoptosis did not become apparent until 24 h after exposure. Data from six volunteers with different ex vivo doses and post-exposure times were used to test the capability of the combined assay. Results show that simultaneous analysis of gamma-H2AX and radiation-induced apoptosis may provide a rapid and more accurate triage tool in situations where the delay between exposure and blood sampling is unknown compared to gamma-H2AX alone. This combined approach may improve the accuracy of dose estimations in cases where blood sampling is performed days after the radiation exposure.
- Subjects :
- Adult
Aged
Apoptosis radiation effects
Dose-Response Relationship, Radiation
Enzyme Activation radiation effects
Humans
Lymphocyte Subsets cytology
Middle Aged
Tumor Suppressor p53-Binding Protein 1
Young Adult
Caspases metabolism
Histones metabolism
Intracellular Signaling Peptides and Proteins metabolism
Lymphocyte Subsets metabolism
Lymphocyte Subsets radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1938-5404
- Volume :
- 180
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Radiation research
- Publication Type :
- Academic Journal
- Accession number :
- 24219325
- Full Text :
- https://doi.org/10.1667/RR13342.1