Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model.

MedStar author(s):
Citation: Genes (Basel). 13(3), 2022 03 18.PMID: 35328091Institution: MedStar Health Research Institute | MedStar Washington Hospital CenterDepartment: Firefighters' Burn and Surgical Research Laboratory | Surgery/Burn ServicesForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, Non-U.S. Gov'tSubject headings: *Skin | *Transcriptome | Animals | Animals | Biopsy | Disease Models, Animal | Mice | Signal Transduction | Skin/re [Radiation Effects]Year: 2022ISSN:
  • 2073-4425
Name of journal: GenesAbstract: The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p <= 0.05 and FC >= 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications.All authors: Alkhalil A, Clifford J, Gautam A, Hammamieh R, Jett M, Miller SA, Moffatt LT, Shupp JWOriginally published: Genes (Basel). 13(3), 2022 03 18.Fiscal year: FY2022Digital Object Identifier: Date added to catalog: 2022-05-11
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Journal Article MedStar Authors Catalog Article 35328091 Available 35328091

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p <= 0.05 and FC >= 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications.

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