Combined analysis of gamma-H2AX/53BP1 foci and caspase activation in lymphocyte subsets detects recent and more remote radiation exposures
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Combined analysis of gamma-H2AX/53BP1 foci and caspase activation in lymphocyte subsets detects recent and more remote radiation exposures. / Horn, Simon; Barnard, Stephen; Brady, Darren; Prise, Kevin M; Rothkamm, Kai.
In: RADIAT RES, Vol. 180, No. 6, 12.2013, p. 603-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Combined analysis of gamma-H2AX/53BP1 foci and caspase activation in lymphocyte subsets detects recent and more remote radiation exposures
AU - Horn, Simon
AU - Barnard, Stephen
AU - Brady, Darren
AU - Prise, Kevin M
AU - Rothkamm, Kai
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Apoptosis/radiation effects
KW - Caspases/metabolism
KW - Dose-Response Relationship, Radiation
KW - Enzyme Activation/radiation effects
KW - Histones/metabolism
KW - Humans
KW - Intracellular Signaling Peptides and Proteins/metabolism
KW - Lymphocyte Subsets/cytology
KW - Middle Aged
KW - Tumor Suppressor p53-Binding Protein 1
KW - Young Adult
U2 - 10.1667/RR13342.1
DO - 10.1667/RR13342.1
M3 - SCORING: Journal article
C2 - 24219325
VL - 180
SP - 603
EP - 609
IS - 6
ER -