Follow-up of stable chromosomal aberrations in gamma-ray irradiated non-human primates

Grégoire, Éric; Sorokine-Durm, I.; Bertho, Jean-Marc; Jacquet, N.; Delbos, M; Demarquay, Christelle; Voisin, Philippe; Roy, Laurence

doi:10.1080/09553000600840930

Cited by 14 publications

(6 citation statements)

References 28 publications

(34 reference statements)

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“…Non-human primate model systems of study also exhibit radiation-induced depletion. Tn particular, Macaca fascicularis can exhibit a 70% depletion of total lymphocytes 24 h after 2 and 4 Gy irradiation (29). These findings harmonize with depletion effects seen also in human subjects of study.…”

Section: Discussionsupporting

confidence: 79%

Use of a Humanized Mouse Model System in the Validation of Human Radiation Biodosimetry Standards

2019

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After a planned or unplanned radiation exposure, determination of absorbed dose has great clinical importance, informing treatment and triage decisions in the exposed individuals. Biodosimetry approaches allow for determination of dose in the absence of physical measurement apparatus. The current state-of-the-art biodosimetry method is based on the frequency of induced dicentric chromosomes in peripheral blood T cells, which is proportional to the absorbed radiation dose. Since dose-response curves used for obtaining absorbed dose for humans are based on data sourced from in vitro studies, a concerning discrepancy may be present in the reported dose. Specifically, T-cell survival after in vitro irradiation is much higher than that measured in humans in vivo and, in addition, is not dose dependent over some dose ranges. We hypothesized that these differences may lead to inappropriately inflated dicentric frequencies after in vitro irradiation when compared with in vivo irradiation of the same samples. This may lead to underestimation of the in vivo dose. To test this hypothesis, we employed the humanized mouse model, which allowed direct comparison of cell depletion and dicentric frequencies in human T cells irradiated in vivo and in vitro. The results showed similar dicentric chromosome induction frequencies measured in vivo and in vitro when assessed 24 h postirradiation despite the differences in cell survival. These results appear to validate the use of in vitro data for the estimation of the absorbed dose in human radiation biodosimetry.

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Section: Discussionsupporting

confidence: 79%

Use of a Humanized Mouse Model System in the Validation of Human Radiation Biodosimetry Standards

2019

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“…These results are encouraging for the utility of the MNi biomarker in a partial body, long-term animal model. Previously, Gregoire et al reported elevated translocation and dicentric chromosome frequencies in blood samples from total body gamma ray irradiated NHPs up to 31 months after irradiation [ 50 ] and Thierens et al were able to derive dose estimates from dicentrics chromosomes and micronucleus frequencies 6 months after an accidental exposure of a radiological worker [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells

et al. 2018

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We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60–100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI.We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

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“…1). Même si quelques études ont montré une décroissance du taux de translocations avec le temps (Bauchinger et al, 2001 ;Lindholm et Edwards, 2004 ;Sorokine-Durm et al, 2000a ;Tucker, 2008), la stabilité des translocations est incontestablement meilleure que celle des dicentriques Grégoire et al, 2006 ;Lindholm et Edwards, 2004 ;Pala et al, 2001 ;Tawn et al, 2006 ;Tucker, 2008). L'étude de patients traités par radiothérapie durant des dizaines d'années pour spondylarthrite ankylosante, suggère que les translocations semblent persister plusieurs années après l'exposition (Buckton et al, 1962).…”

Section: Introductionunclassified

Impact des facteurs individuels et environnementaux sur le taux d’aberrations chromosomiques de type translocations Partie 1 : âge, sexe, tabac, alcool

et al. 2010

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The assessment of exposure to ionizing radiation, carried out long time after exposure, is currently performed by scoring of translocations, a specific type of chromosomal aberrations. The translocations rate observed in peripheral blood lymphocytes of exposed subjects is compared to that observed in a control population. However, the translocation specificity towards radiation exposure is not clearly identified. To avoid any hasty conclusion, it is necessary to identify all the factors likely to induce translocation. To our knowledge, no study has thus far examined the effects of all these different factors on translocation rates. A review of the literature thus allowed us to assess the impact of host factors and lifestyle on the production of translocations. This study confirms that age appears to be the factor 1 IRSN, Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay-aux-Roses Cedex, France.Article publié par EDP Sciences E. GRÉGOIRE et al. 154 RADIOPROTECTION -VOL. 45 -N° 2 (2010) having the greatest impact on the rate of translocations, especially over 60 years. To date, the factor "age" is already considered in estimating the impact of radiation on the rate of translocation for all age groups. However, the study also shows that this rate varies significantly when the patient is exposed simultaneously and significantly towards many lifestyle agents. A precise threshold translocation rate should thus be established as a function of known behavioral exposures, below which it is impossible to conclude that radiological exposure has occurred. The effects of chemicals on the translocation rate after occupational exposure will be the subject of a second part.

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Follow-up of stable chromosomal aberrations in gamma-ray irradiated non-human primates

Cited by 14 publications

References 28 publications

Use of a Humanized Mouse Model System in the Validation of Human Radiation Biodosimetry Standards

Use of a Humanized Mouse Model System in the Validation of Human Radiation Biodosimetry Standards

Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells

Impact des facteurs individuels et environnementaux sur le taux d’aberrations chromosomiques de type translocations Partie 1 : âge, sexe, tabac, alcool

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