Comparison of established and emerging biodosimetry assays
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Comparison of established and emerging biodosimetry assays. / Rothkamm, K; Beinke, C; Romm, H; Badie, C; Balagurunathan, Y; Barnard, S; Bernard, N; Boulay-Greene, H; Brengues, M; De Amicis, A; De Sanctis, S; Greither, R; Herodin, F; Jones, A; Kabacik, S; Knie, T; Kulka, U; Lista, F; Martigne, P; Missel, A; Moquet, J; Oestreicher, U; Peinnequin, A; Poyot, T; Roessler, U; Scherthan, H; Terbrueggen, B; Thierens, H; Valente, M; Vral, A; Zenhausern, F; Meineke, V; Braselmann, H; Abend, M.
In: RADIAT RES, Vol. 180, No. 2, 08.2013, p. 111-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Comparison of established and emerging biodosimetry assays
AU - Rothkamm, K
AU - Beinke, C
AU - Romm, H
AU - Badie, C
AU - Balagurunathan, Y
AU - Barnard, S
AU - Bernard, N
AU - Boulay-Greene, H
AU - Brengues, M
AU - De Amicis, A
AU - De Sanctis, S
AU - Greither, R
AU - Herodin, F
AU - Jones, A
AU - Kabacik, S
AU - Knie, T
AU - Kulka, U
AU - Lista, F
AU - Martigne, P
AU - Missel, A
AU - Moquet, J
AU - Oestreicher, U
AU - Peinnequin, A
AU - Poyot, T
AU - Roessler, U
AU - Scherthan, H
AU - Terbrueggen, B
AU - Thierens, H
AU - Valente, M
AU - Vral, A
AU - Zenhausern, F
AU - Meineke, V
AU - Braselmann, H
AU - Abend, M
PY - 2013/8
Y1 - 2013/8
N2 - Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools.
AB - Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools.
KW - Adult
KW - Biological Assay/methods
KW - Cells, Cultured/drug effects
KW - Chromosome Aberrations
KW - Chromosomes, Human/radiation effects
KW - Cytokinesis/radiation effects
KW - DNA Breaks, Double-Stranded/radiation effects
KW - Dose-Response Relationship, Radiation
KW - Gene Expression/radiation effects
KW - Histones/metabolism
KW - Humans
KW - Laboratory Proficiency Testing
KW - Leukocytes/radiation effects
KW - Male
KW - Micronucleus Tests
KW - Phosphorylation
KW - Protein Processing, Post-Translational
KW - Radiation Injuries/diagnosis
KW - Radioactive Hazard Release
KW - Radiometry/methods
KW - Reproducibility of Results
KW - Sensitivity and Specificity
KW - Single-Blind Method
KW - Time Factors
KW - Triage/methods
U2 - 10.1667/RR3231.1
DO - 10.1667/RR3231.1
M3 - SCORING: Journal article
C2 - 23862692
VL - 180
SP - 111
EP - 119
IS - 2
ER -
