G-PCC-FISH Derived Multi-parametric Biodosimetry Methodology for Accidental High Dose and Partial Body Exposures

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jul 12

PMID 38997265

Authors

Usha Yadav

Nagesh N Bhat

Utkarsha S Mungse

Kapil B Shirsath

Manish Joshi

Balvinder K Sapra

Affiliations

Soon will be listed here.

Abstract

High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G-PCC-FISH, Dolphin's approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G-PCC-Fragment assay (conventional G-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G-PCC-FISH was found to be most accurate for the dose estimation. G-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.

References

Yadav U, Bhat N, Shirsaath K, Mungse U, Sapra B . Refined premature chromosome condensation (G-PCC) with cryo-preserved mitotic cells for rapid radiation biodosimetry. Sci Rep. 2021; 11(1):13498. PMC: 8242027. DOI: 10.1038/s41598-021-92886-6. View

Pereira de Lemos Pinto M, Santos N, Amaral A . Current status of biodosimetry based on standard cytogenetic methods. Radiat Environ Biophys. 2010; 49(4):567-81. DOI: 10.1007/s00411-010-0311-3. View

Lamadrid Boada A, Romero Aguilera I, Terzoudi G, Gonzalez Mesa J, Pantelias G, Garcia O . Rapid assessment of high-dose radiation exposures through scoring of cell-fusion-induced premature chromosome condensation and ring chromosomes. Mutat Res. 2013; 757(1):45-51. DOI: 10.1016/j.mrgentox.2013.06.021. View

Karachristou I, Karakosta M, Pantelias A, Hatzi V, Karaiskos P, Dimitriou P . Triage biodosimetry using centromeric/telomeric PNA probes and Giemsa staining to score dicentrics or excess fragments in non-stimulated lymphocyte prematurely condensed chromosomes. Mutat Res Genet Toxicol Environ Mutagen. 2015; 793:107-14. DOI: 10.1016/j.mrgentox.2015.06.013. View

Blakely W, Prasanna P, Kolanko C, Pyle M, Mosbrook D, Loats A . Application of the premature chromosome condensation assay in simulated partial-body radiation exposures: evaluation of the use of an automated metaphase-finder. Stem Cells. 1995; 13 Suppl 1:223-30. View

Darroudi F, Fomina J, Meijers M, Natarajan A . Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes, using PCC and FISH. Mutat Res. 1998; 404(1-2):55-65. DOI: 10.1016/s0027-5107(98)00095-5. View

Rao B, Natarajan A . Retrospective biological dosimetry of absorbed radiation. Radiat Prot Dosimetry. 2001; 95(1):17-23. DOI: 10.1093/oxfordjournals.rpd.a006516. View

Hatzi V, Terzoudi G, Paraskevopoulou C, Makropoulos V, Matthopoulos D, Pantelias G . The use of premature chromosome condensation to study in interphase cells the influence of environmental factors on human genetic material. ScientificWorldJournal. 2006; 6:1174-90. PMC: 5917154. DOI: 10.1100/tsw.2006.210. View

Kanda R, Hayata I, Lloyd D . Easy biodosimetry for high-dose radiation exposures using drug-induced, prematurely condensed chromosomes. Int J Radiat Biol. 2001; 75(4):441-6. DOI: 10.1080/095530099140366. View

10.

Lindholm C, Stricklin D, Jaworska A, Koivistoinen A, Paile W, Arvidsson E . Premature chromosome condensation (PCC) assay for dose assessment in mass casualty accidents. Radiat Res. 2010; 173(1):71-8. DOI: 10.1667/RR1843.1. View

11.

Sproull M, Camphausen K, Koblentz G . Biodosimetry: A Future Tool for Medical Management of Radiological Emergencies. Health Secur. 2017; 15(6):599-610. PMC: 5734138. DOI: 10.1089/hs.2017.0050. View

12.

Yadav U, Bhat N, Shirsath K, Mungse U, Sapra B . Multifaceted applications of pre-mature chromosome condensation in radiation biodosimetry. Int J Radiat Biol. 2020; 96(10):1274-1280. DOI: 10.1080/09553002.2020.1798545. View

13.

Pantelias G, Maillie H . The use of peripheral blood mononuclear cell prematurely condensed chromosomes for biological dosimetry. Radiat Res. 1984; 99(1):140-50. View

14.

Ryan T, Pantelias A, Terzoudi G, Pantelias G, Balajee A . Use of human lymphocyte G0 PCCs to detect intra- and inter-chromosomal aberrations for early radiation biodosimetry and retrospective assessment of radiation-induced effects. PLoS One. 2019; 14(5):e0216081. PMC: 6502328. DOI: 10.1371/journal.pone.0216081. View

15.

Pantelias G, Maillie H . A simple method for premature chromosome condensation induction in primary human and rodent cells using polyethylene glycol. Somatic Cell Genet. 1983; 9(5):533-47. DOI: 10.1007/BF01574257. View

16.

Balakrishnan S, Shirsath K, Bhat N, Anjaria K . Biodosimetry for high dose accidental exposures by drug induced premature chromosome condensation (PCC) assay. Mutat Res. 2010; 699(1-2):11-6. DOI: 10.1016/j.mrgentox.2010.03.008. View

17.

Durante M, George K, Yang T . Biological dosimetry by interphase chromosome painting. Radiat Res. 1996; 145(1):53-60. View

18.

Fomina J, Darroudi F, Natarajan A . Accurate detection of true incomplete exchanges in human lymphocytes exposed to neutron radiation using chromosome painting in combination with a telomeric PNA probe. Int J Radiat Biol. 2001; 77(12):1175-83. DOI: 10.1080/09553000110083951. View

19.

Shuryak I, Turner H, Perrier J, Cunha L, Canadell M, Durrani M . A High Throughput Approach to Reconstruct Partial-Body and Neutron Radiation Exposures on an Individual Basis. Sci Rep. 2020; 10(1):2899. PMC: 7031285. DOI: 10.1038/s41598-020-59695-9. View

20.

Shen X, Ma T, Li C, Wen Z, Zheng J, Zhou Z . High-precision automatic identification method for dicentric chromosome images using two-stage convolutional neural network. Sci Rep. 2023; 13(1):2124. PMC: 9902391. DOI: 10.1038/s41598-023-28456-9. View