Abstract
Biodosimetry-based individualized reconstruction of complex irradiation scenarios (partial-body shielding and/or neutron + photon mixtures) can improve treatment decisions after mass-casualty radiation-related incidents. We used a high-throughput micronucleus assay with automated scanning and imaging software on ex-vivo irradiated human lymphocytes to: a) reconstruct partial-body and/or neutron exposure, and b) estimate separately the photon and neutron doses in a mixed exposure. The mechanistic background is that, compared with total-body photon irradiations, neutrons produce more heavily-damaged lymphocytes with multiple micronuclei/binucleated cell, whereas partial-body exposures produce fewer such lymphocytes. To utilize these differences for biodosimetry, we developed metrics that describe micronuclei distributions in binucleated cells and serve as predictors in machine learning or parametric analyses of the following scenarios: (A) Homogeneous gamma-irradiation, mimicking total-body exposures, vs. mixtures of irradiated blood with unirradiated blood, mimicking partial-body exposures. (B) X rays vs. various neutron + photon mixtures. The results showed high accuracies of scenario and dose reconstructions. Specifically, receiver operating characteristic curve areas (AUC) for sample classification by exposure type reached 0.931 and 0.916 in scenarios A and B, respectively. R2 for actual vs. reconstructed doses in these scenarios reached 0.87 and 0.77, respectively. These encouraging findings demonstrate a proof-of-principle for the proposed approach of high-throughput reconstruction of clinically-relevant complex radiation exposure scenarios.
Highlights
The dicentric chromosome (DCA) and the cytokinesis-block micronucleus (CBMN) assays represent established and robust radiation biodosimetry tools because of low background yields in unirradiated individuals and reliable dose responses after exposure to ionizing radiation
Our intention was to utilize the information contained in the shapes of probability distributions for micronuclei/binucleated cell counts in peripheral blood lymphocytes to develop a CBMN-based methodology for high-throughput automatic discrimination of complex irradiation scenarios like partial-body shielding and/or neutron + photon mixtures from simpler exposures such as homogeneous total-body photon irradiation[2,21,22]
The distribution of micronuclei per cell for a 1:1 mixture of 4 Gy irradiated blood with 0 Gy unirradiated blood was different from the distribution for blood irradiated with 2 Gy of pure gamma rays (Fig. 2), despite the fact that the mean micronuclei yields per binucleated cell were similar for these two scenarios (0.20 vs. 0.22, respectively)
Summary
The dicentric chromosome (DCA) and the cytokinesis-block micronucleus (CBMN) assays represent established and robust radiation biodosimetry tools because of low background yields in unirradiated individuals and reliable dose responses after exposure to ionizing radiation. Our intention was to utilize the information contained in the shapes of probability distributions for micronuclei/binucleated cell counts in peripheral blood lymphocytes to develop a CBMN-based methodology for high-throughput automatic discrimination of complex irradiation scenarios like partial-body shielding and/or neutron + photon mixtures from simpler exposures such as homogeneous total-body photon irradiation[2,21,22]. Such a capability for rapid individualized reconstruction of exposure type on a large scale is important for making appropriate triage and treatment decisions in mass casualty situations. It is likely that different countermeasures will be required for neutron-induced vs photon-induced disease[30]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
