Retrospective biodosimetry techniques: Focus on cytogenetics assays for individuals exposed to ionizing radiation

Hérate, Cécile; Sabatier, Laure

doi:10.1016/j.mrrev.2019.108287

Cited by 24 publications

(12 citation statements)

References 158 publications

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“…However, it should be noted that the majority of the total dose received by an individual will be due to external exposure [ 8 ]. Cytogenetic analysis [ 9 ], the current gold standard for radiation assessment, remains laborious and time consuming, while newer methods, such as automated γ-H2AX foci counting and gene expression have shown potential in evaluating dose rate effects through internal emitters [ 10 , 11 , 12 ]. Recently, metabolomics has emerged as a method to determine biological dose and dose rate effects by assessing biofluids and developing biomarkers and biosignatures [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates

Lin

Laiakis

et al. 2020

Metabolites

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Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples from mice exposed to 137Cs internal emitters. Animals were injected intraperitoneally with 137CsCl solutions of varying radioactivity, and the absorbed doses were calculated. To determine the dose rate effect, serum samples were collected at 2, 3, 5, 7, and 14 days after injection. Based on the time for each group receiving the cumulative dose of 4 Gy, the dose rate for each group was determined. The dose rates analyzed were 0.16 Gy/day (low), 0.69 Gy/day (medium), and 1.25 Gy/day (high). The results indicated that at a cumulative dose of 4 Gy, the low dose rate group had the least number of statistically significantly differential spectral features. Some identified metabolites showed common changes for different dose rates. For example, significantly altered levels of oleamide and sphingosine 1-phosphate were seen in all three groups. On the other hand, the intensity of three amino acids, Isoleucine, Phenylalanine and Arginine, significantly decreased only in the medium dose rate group. These findings have the potential to be used in assessing the exposure and the biological effects of internal emitters.

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Section: Introductionmentioning

confidence: 99%

Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates

Lin

Laiakis

et al. 2020

Metabolites

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“…In this study, the authors employed dicentric chromosome as a marker of interchromosomal CR. Similar to translocation, dicentric is a type of interchromosomal SV that occurs when two broken chromosomes are rejoined erroneously (Figure 1) [90]. Translocation and dicentric formation are known to occur at similar frequencies [89,91].…”

Section: Mechanisms Underlying the Atm-dependent Suppression Of Cr At Immune Gene Locimentioning

confidence: 99%

Mechanisms Underlying the Suppression of Chromosome Rearrangements by Ataxia-Telangiectasia Mutated

Yamauchi

2021

Genes

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Chromosome rearrangements are structural variations in chromosomes, such as inversions and translocations. Chromosome rearrangements have been implicated in a variety of human diseases. Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by a broad range of clinical and cellular phenotypes. At the cellular level, one of the most prominent features of A-T cells is chromosome rearrangement, especially that in T lymphocytes. The gene that is defective in A-T is ataxia-telangiectasia mutated (ATM). The ATM protein is a serine/threonine kinase and plays a central role in the cellular response to DNA damage, particularly DNA double-strand breaks. In this review, the mechanisms by which ATM suppresses chromosome rearrangements are discussed.

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“…Furthermore, unexpected human exposure to radiation can occur due to attacks with atomic bombs. The prompt and accurate identification and quantification of the dose and radiation quality, an individual was exposed to, is essential for the initial medical assessment and treatment decision 2 , 3 . Especially in cases where the exposed human did not wear a dosimeter, or when there are discrepancies between the technical measurements using dosimeters and occurring radiation injuries, additional biological dosimetry methods are necessary 4 .…”

Section: Introductionmentioning

confidence: 99%

Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters

Reindl

Kundrát

Girst

et al. 2022

Sci Rep

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The human body is constantly exposed to ionizing radiation of different qualities. Especially the exposure to high-LET (linear energy transfer) particles increases due to new tumor therapy methods using e.g. carbon ions. Furthermore, upon radiation accidents, a mixture of radiation of different quality is adding up to human radiation exposure. Finally, long-term space missions such as the mission to mars pose great challenges to the dose assessment an astronaut was exposed to. Currently, DSB counting using γH2AX foci is used as an exact dosimetric measure for individuals. Due to the size of the γH2AX IRIF of ~ 0.6 µm, it is only possible to count DSB when they are separated by this distance. For high-LET particle exposure, the distance of the DSB is too small to be separated and the dose will be underestimated. In this study, we developed a method where it is possible to count DSB which are separated by a distance of ~ 140 nm. We counted the number of ionizing radiation-induced pDNA-PKcs (DNA-PKcs phosphorylated at T2609) foci (size = 140 nm ± 20 nm) in human HeLa cells using STED super-resolution microscopy that has an intrinsic resolution of 100 nm. Irradiation was performed at the ion microprobe SNAKE using high-LET 20 MeV lithium (LET = 116 keV/µm) and 27 MeV carbon ions (LET = 500 keV/µm). pDNA-PKcs foci label all DSB as proven by counterstaining with 53BP1 after low-LET γ-irradiation where separation of individual DSB is in most cases larger than the 53BP1 gross size of about 0.6 µm. Lithium ions produce (1.5 ± 0.1) IRIF/µm track length, for carbon ions (2.2 ± 0.2) IRIF/µm are counted. These values are enhanced by a factor of 2–3 compared to conventional foci counting of high-LET tracks. Comparison of the measurements to PARTRAC simulation data proof the consistency of results. We used these data to develop a measure for dosimetry of high-LET or mixed particle radiation exposure directly in the biological sample. We show that proper dosimetry for radiation up to a LET of 240 keV/µm is possible.

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Retrospective biodosimetry techniques: Focus on cytogenetics assays for individuals exposed to ionizing radiation

Cited by 24 publications

References 158 publications

Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates

Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates

Mechanisms Underlying the Suppression of Chromosome Rearrangements by Ataxia-Telangiectasia Mutated

Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters

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