Rat Models of Partial-body Irradiation with Bone Marrow-sparing (Leg-out PBI) Designed for FDA Approval of Countermeasures for Mitigation of Acute and Delayed Injuries by Radiation.
Journal
Health physics
ISSN: 1538-5159
Titre abrégé: Health Phys
Pays: United States
ID NLM: 2985093R
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
entrez:
21
9
2021
pubmed:
22
9
2021
medline:
15
3
2022
Statut:
ppublish
Résumé
The goal of this study was to develop rat models of partial body irradiation with bone-marrow sparing (leg-out PBI) to test medical countermeasures (MCM) of both acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE) under the FDA animal rule. The leg-out PBI models were developed in female and male WAG/RijCmcr rats at doses of 12.5-14.5 Gy. Rats received supportive care consisting of fluids and antibiotics. Gastrointestinal ARS (GI-ARS) was assessed by lethality to d 7 and diarrhea scoring to d 10. Differential blood counts were analyzed between d 1-42 for the natural history of hematopoietic ARS (H-ARS). Lethality and breathing intervals (BI) were measured between d 28-110 to assess delayed injury to the lung (L-DEARE). Kidney injury (K-DEARE) was evaluated by measuring elevation of blood urea nitrogen (BUN) between d 90-180. The LD50/30, including both lethality from GI-ARS and H-ARS, for female and male rats are 14.0 Gy and 13.5 Gy, respectively, while the LD50/7 for only GI-ARS are 14.3 Gy and 13.6 Gy, respectively. The all-cause mortalities, including ARS and L-DEARE, through 120 d (LD50/120) are 13.5 Gy and 12.9 Gy, respectively. Secondary end points confirmed occurrence of four distinct sequelae representing GI, hematopoietic, lung, and kidney toxicities after leg-out PBI. Adult rat models of leg-out PBI showed the acute and long-term sequelae of radiation damage that has been reported in human radiation exposure case studies. Sex-specific differences were observed in the DRR between females and males. These rat models are among the most useful for the development and approval of countermeasures for mitigation of radiation injuries under the FDA animal rule.
Identifiants
pubmed: 34546222
doi: 10.1097/HP.0000000000001444
pii: 00004032-202110000-00011
pmc: PMC8577554
mid: NIHMS1693731
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
419-433Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201800012C
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI107305
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI133594
Pays : United States
Informations de copyright
Copyright © 2021 Health Physics Society.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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