Bridging the gaps: using an NHP model to predict single dose radiation absorption in humans

Iversen, Edwin S.; McCarthy, Janice; Burdett, Kirsten Bell; Lipton, Gary; Phillips, Gary; Dressman, Holly K.; Ross, Joel; Chao, Nelson J.

doi:10.1080/09553002.2018.1532614

Cited by 7 publications

(3 citation statements)

References 8 publications

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“…Globin-cleared RNA samples were hybridized to Agilent Whole Genome Human 4X44 v2 (catalog number: G4845A) microarrays using the manufacturer’s protocol, based on inter-species cross reactivity microarray tests between H. sapiens and Macaca mulatta [ 63 , 64 ]. Feature extraction of the images was performed using Agilent’s FE version 10.7 software and data were imported into BRB ArrayTools software version 4.6.0.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques

et al. 2023

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Background Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. Results The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiated earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGFβ and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27–0.33 up to 28 days and declined to 0.1 by day 56. Conclusions Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.

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Section: Methodsmentioning

confidence: 99%

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques

et al. 2023

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“…Point-of-care tools are needed for rapid triage to identify exposed victims shortly after an incident, while high throughput diagnostic tests are essential for dose stratification such that the appropriate medical support can be provided while taking into account logistical considerations. The utility of using radiation-responsive protein (Balog et al 2019) and gene expression signatures (Iversen et al 2019;Jacobs et al 2019) in diagnostic devices are discussed in this volume.…”

Section: Editorialmentioning

confidence: 99%

Non-clinical radiation biology and pharmacology models: appraisal of state-of-the-art and innovation

Authier¹,

Cassatt

Chang

2019

International Journal of Radiation Biology

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“…In the near 15 years since its initiation, this Program has funded several institutions as centers of excellence, although the number of centers has declined across the intervening years from an original 8 (in which this review's senior author was a funded participant) to the current 4. This focused effort has resulted in many advances in the field as a whole, for example in animal model characterization (Williams et al 2010;Iversen et al 2018), the development of biodosimetry technologies (Brenner et al 2015;Flood et al 2016;Repin et al 2017;Jacobs et al 2018) and identification of potential biomarkers of exposure (DeBo et al 2015;Himburg et al 2016;Laiakis et al 2016;Lee et al 2018). Unfortunately, however, there does not yet appear to have been a significant breakthrough in countermeasure development per se by the Program, at least at the level of agents entering human trials.…”

Section: Current State Of Play (2013-2018)mentioning

confidence: 99%

Saving normal tissues – a goal for the ages

Groves

Williams

2019

International Journal of Radiation Biology

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Purpose: Almost since the earliest utilization of ionizing radiation, many within the radiation community have worked towards either preventing (i.e. protecting) normal tissues from unwanted radiation injury or rescuing them from the downstream consequences of exposure. However, despite over a century of such investigations, only incremental gains have been made towards this goal and, with certainty, no outright panacea having been found. In celebration of the 60 th anniversary of the International Journal of Radiation Biology and to chronicle the efforts that have been made to date, we undertook a non-rigorous survey of the articles published by normal tissue researchers in this area, using those that have appeared in the aforementioned journal as a road map. Three 'snapshots' of publications on normal tissue countermeasures were taken: the earliest (1959-1963) and most recent (2013-2018) 5-years of issues, as well as a 5-year intermediate span (1987-1991). Conclusions: Limiting the survey solely to articles appearing within International Journal of Radiation Biology likely reduced the number of translational studies interrogated given the basic science tenor of this particular publication. In addition, by taking 'snapshots' rather than considering the entire breadth of the journal's history in this field, important papers that were published during the interim periods were omitted, for which we apologize. Nonetheless, since the journal's inception, we observed that, during the chosen periods, the majority of studies undertaken in the field of normal tissue countermeasures, whether investigating radiation protectants, mitigators or treatments, have focused on agents that interfere with the physical, chemical and/or biological effects known to occur during the acute period following whole body/ high single dose exposures. This relatively narrow approach to the reduction of normal tissue effects, especially those that can take months, if not years, to develop, seems to contradict our growing understanding of the progressive complexities of the microenvironmental disruption that follows the initial radiation injury. Given the analytical tools now at our disposal and the enormous benefits that may be reaped in terms of improving patient outcomes, as well as the potential for

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Bridging the gaps: using an NHP model to predict single dose radiation absorption in humans

Cited by 7 publications

References 8 publications

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques

Non-clinical radiation biology and pharmacology models: appraisal of state-of-the-art and innovation

Saving normal tissues – a goal for the ages

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