title: Comparison of established and emerging biodosimetry assays.
abstract: 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.
authors.affiliation: Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon OX11 0RQ, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Rothkamm
authors.forename: C
authors.initials: C
authors.lastname: Beinke
authors.forename: H
authors.initials: H
authors.lastname: Romm
authors.forename: C
authors.initials: C
authors.lastname: Badie
authors.forename: Y
authors.initials: Y
authors.lastname: Balagurunathan
authors.forename: S
authors.initials: S
authors.lastname: Barnard
authors.forename: N
authors.initials: N
authors.lastname: Bernard
authors.forename: H
authors.initials: H
authors.lastname: Boulay-Greene
authors.forename: M
authors.initials: M
authors.lastname: Brengues
authors.forename: A
authors.initials: A
authors.lastname: De Amicis
authors.forename: S
authors.initials: S
authors.lastname: De Sanctis
authors.forename: R
authors.initials: R
authors.lastname: Greither
authors.forename: F
authors.initials: F
authors.lastname: Herodin
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Kabacik
authors.forename: T
authors.initials: T
authors.lastname: Knie
authors.forename: U
authors.initials: U
authors.lastname: Kulka
authors.forename: F
authors.initials: F
authors.lastname: Lista
authors.forename: P
authors.initials: P
authors.lastname: Martigne
authors.forename: A
authors.initials: A
authors.lastname: Missel
authors.forename: J
authors.initials: J
authors.lastname: Moquet
authors.forename: U
authors.initials: U
authors.lastname: Oestreicher
authors.forename: A
authors.initials: A
authors.lastname: Peinnequin
authors.forename: T
authors.initials: T
authors.lastname: Poyot
authors.forename: U
authors.initials: U
authors.lastname: Roessler
authors.forename: H
authors.initials: H
authors.lastname: Scherthan
authors.forename: B
authors.initials: B
authors.lastname: Terbrueggen
authors.forename: H
authors.initials: H
authors.lastname: Thierens
authors.forename: M
authors.initials: M
authors.lastname: Valente
authors.forename: A
authors.initials: A
authors.lastname: Vral
authors.forename: F
authors.initials: F
authors.lastname: Zenhausern
authors.forename: V
authors.initials: V
authors.lastname: Meineke
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: M
authors.initials: M
authors.lastname: Abend
mesh_terms: D000328:Adult; D001681:Biological Assay / Q000379:methods*; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects*; D048749:Cytokinesis / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D059021:Laboratory Proficiency Testing; D007962:Leukocytes / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D015162:Micronucleus Tests; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011832:Radiation Injuries / Q000175:diagnosis / Q000235:genetics; D018788:Radioactive Hazard Release; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D013997:Time Factors; D014218:Triage / Q000379:methods
chemical_list: C468783:H2AX protein, human; D006657:Histones