Interlaboratory Variation in Scoring Dicentric Chromosomes in a Case of Partial-Body X-Ray Exposure: Implications for Biodosimetry Networking and Cytogenetic “Triage Mode” Scoring

Ainsbury, Elizabeth A.; Livingston, Gordon K.; Abbott, Mick; Moquet, Jayne; Hone, P. A.; Jenkins, Mark S.; Christensen, Doran M.; Lloyd, David; Rothkamm, Kai

doi:10.1667/rr1934.1

Cited by 30 publications

(17 citation statements)

References 12 publications

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“…The results confirmed the previous investigations with the 8-h post-irradiation incubation time (Pantelias et al 1993;Greinert et al 1995). It is obvious that the accuracy of the estimated dose increases by increasing the number of scored cells (Ainsbury et al 2009;Romm et al 2011). It should be noted that the PCDC assay may allow dose estimates to be obtained in 1 day after blood collection.…”

Section: Resultssupporting

confidence: 88%

Assessing the Applicability of FISH-based Prematurely Condensed Dicentric Chromosome Assay in Triage Biodosimetry

Suto¹,

Gotoh²,

Noda³

et al. 2015

Health Physics

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The dicentric chromosome assay (DCA) has been regarded as the gold standard of radiation biodosimetry. The assay, however, requires a 2-d peripheral blood lymphocyte culture before starting metaphase chromosome analyses to estimate biological doses. Other biological assays also have drawbacks with respect to the time needed to obtain dose estimates for rapid decision on the correct line of medical treatment. Therefore, alternative technologies that suit requirements for triage biodosimetry are needed. Radiation-induced DNA double strand breaks in G0 lymphocytes can be detected as interphase chromosome aberrations by the cell fusion-mediated premature chromosome condensation (PCC) method. The method, in combination with fluorescence in situ hybridization (FISH) techniques, has been proposed in early studies as a powerful tool for obtaining biological dose estimates without 2-d lymphocyte culture procedures. The present work assesses the applicability of FISH-based PCC techniques using pan-centromeric and telomeric peptide nucleic acid (PNA) probes in triage mode biodosimetry and demonstrates that an improved rapid procedure of the prematurely condensed dicentric chromosome (PCDC) assay has the potential for evaluating exposed radiation doses in as short as 6 h after the collection of peripheral blood specimens.

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Section: Resultssupporting

confidence: 88%

Assessing the Applicability of FISH-based Prematurely Condensed Dicentric Chromosome Assay in Triage Biodosimetry

Suto¹,

Gotoh²,

Noda³

et al. 2015

Health Physics

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“…Only the DCA and γ-H2AX assay but not the other methods have been formally shown to be able to detect and quantify nonuniform exposures in certain scenarios, based on the distribution of dicentrics or foci, respectively, among analyzed cells (3, 25, 29, 30). Even then, the low number of cells scored in triage mode may pose difficulties in the case of highly nonuniform exposures (31). More data and better statistical methods are needed to fully understand the impact of nonuniform exposures on biological dose estimates and associated uncertainties (32).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Established and Emerging Biodosimetry Assays

et al. 2013

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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.

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“…The most probable reason for this was the low numbers of cells scored in the triage mode. A limitation of the triage mode in the evaluation of partial-body irradiation was highlighted recently when the dicentric assay failed in the identification of overdispersion and dose-estimation during the assessment of a patient partially exposed to radiation [13]. …”

Section: Introductionmentioning

confidence: 99%

Assessment of simulated high-dose partial-body irradiation by PCC-R assay

Romero

García

Lamadrid

et al. 2013

Journal of Radiation Research

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The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0–20 Gy, with 60Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10–90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth's u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D0 value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10–20 Gy, and the initial fraction of irradiated cells in the interval from 10–90%.

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Interlaboratory Variation in Scoring Dicentric Chromosomes in a Case of Partial-Body X-Ray Exposure: Implications for Biodosimetry Networking and Cytogenetic “Triage Mode” Scoring

Cited by 30 publications

References 12 publications

Assessing the Applicability of FISH-based Prematurely Condensed Dicentric Chromosome Assay in Triage Biodosimetry

Assessing the Applicability of FISH-based Prematurely Condensed Dicentric Chromosome Assay in Triage Biodosimetry

Comparison of Established and Emerging Biodosimetry Assays

Assessment of simulated high-dose partial-body irradiation by PCC-R assay

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