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Partial-body biodosimetry is likely to be required after a radiological or nuclear exposure. Clinical signs and symptoms, distribution of dicentrics in circulating blood cells, organ-specific biomarkers, and physical signals in teeth and fingernails all can provide indications of non-homogeneous exposures. Organ specific biomarkers may provide early warning regarding physiological systems at risk after radiation injury. Use of a combination of markers and symptoms will be needed for clinical insights for therapeutic approaches. Analysis of dicentrics, a marker specific for radiation injury, is the "gold standard" of biodosimetry and can reveal partial-body exposures. Automation of sample processing for dicentric analysis can increase throughput with customization of off-the-shelf technologies for cytogenetic sample processing and information management. Automated analysis of the metaphase spreads is currently limited, but improvements are in development. The efforts described here bridge the technological gaps to allow the use of dicentric chromosome assay (DCA) for risk-based stratification of mass casualties. This article summarizes current knowledge on partial-body cytogenetic dose assessment, synthesizing information leading to the proposal of an approach to triage dose prediction in radiation mass casualties that is based on equivalent whole-body doses under partial-body exposure conditions and assesses the validity of using this model. An initial screening using only 20 metaphase spreads per subject can confirm irradiation above 2 Gy. A subsequent increase to 50 metaphases improves dose determination to allow risk stratification for clinical triage. Metaphases evaluated for inhomogeneous distribution of dicentrics can reveal partial-body exposures. The authors tested the validity of this approach in an in vitro model that simulates partial-body irradiation by mixing irradiated and un-irradiated lymphocytes in various proportions. Preliminary results support the notion that this approach will be effective under a range of conditions including some partial-body exposures, but may have limitations with low doses or small proportions of irradiated parts of the body. These studies address an important problem in the diagnosis of partial-body irradiation and dose assessment in mass casualties and propose a solution. However, additional work is needed to fully develop and validate the application of DCA to partial-body exposures.

Following a mass-casualty nuclear disaster, effective medical triage has the potential to save tens of thousands of lives. In order to best use the available scarce resources, there is an urgent need for biodosimetry tools to determine an individual's radiation dose. Initial triage for radiation exposure will include location during the incident, symptoms, and physical examination. Stepwise triage will include point of care assessment of less than or greater than 2 Gy, followed by secondary assessment, possibly with high throughput screening, to further define an individual's dose. Given the multisystem nature of radiation injury, it is unlikely that any single biodosimetry assay can be used as a standalone tool to meet the surge in capacity with the timeliness and accuracy needed. As part of the national preparedness and planning for a nuclear or radiological incident, the authors reviewed the primary literature to determine the capabilities and limitations of a number of biodosimetry assays currently available or under development for use in the initial and secondary triage of patients. Understanding the requirements from a response standpoint and the capability and logistics for the various assays will help inform future biodosimetry technology development and acquisition. Factors considered include: type of sample required, dose detection limit, time interval when the assay is feasible biologically, time for sample preparation and analysis, ease of use, logistical requirements, potential throughput, point-of-care capability, and the ability to support patient diagnosis and treatment within a therapeutically relevant time point.

The effective medical management of a suspected acute radiation overexposure incident necessitates recording dynamic medical data, measuring appropriate radiation bioassays, and estimating dose from dosimeters and radioactivity assessments in order to provide diagnostic information to the treating physician and a dose assessment for personnel radiation protection records. The accepted generic multiparameter and early-response approach includes measuring radioactivity and monitoring the exposed individual; observing and recording prodromal signs/symptoms and erythema; obtaining complete blood counts with white blood cell differential; sampling blood for the chromosome-aberration cytogenetic bioassay using the "gold standard" dicentric assay (translocation assay for long times after exposure) for dose assessment; bioassay sampling, if appropriate, to determine radioactivity contamination; and using other available dosimetry approaches. In the event of a radiological mass-casualty incident, current national resources need to be enhanced to provide suitable dose assessment and medical triage and diagnoses. This capability should be broadly based and include stockpiling reagents and devices; establishing deployable (i.e., hematology and biodosimetry) laboratories and reference (i.e., cytogenetic biodosimetry, radiation bioassay) laboratories; networking qualified reference radioactivity-counting bioassay laboratories, cytogenetic biodosimetry, and deployable hematology laboratories with the medical responder community and national radiation protection program; and researching efforts to identify novel radiation biomarkers and develop applied biological dosimetry assays monitored with clinical, deployable, and hand-held analytical systems. These research and applied science efforts should ultimately contribute towards approved, regulated biodosimetry devices or diagnostic tests integrated into a national radioprotection program.

Characterization of the premature chromosome condensation assay for radiation quality is needed. To that end, human lymphocytes were exposed in vitro to various doses of 250-kVp x rays (Y(D) = 4 keV microm(-1), Y(D) is the dose-mean lineal energy of the absorbed dose distribution, D(y), where y is defined as the energy deposited in a volume by a single event divided by the mean chord length of the volume) and to fission neutrons (Y(D) = 65 keV microm(-1)). The distribution of prematurely condensed chromosome and fragments following exposure to x rays or to neutrons were non-Poisson after repair at 37 degrees C for 24 h. Dose-response curves were constructed for the yield of excess prematurely condensed chromosome fragments as necessary for biodosimetry applications. The curves were fitted to a weighted linear model by the least-squares regression method. The neutron relative biological effectiveness (RBE) value was estimated to be 2.4 +/- 0.39.