Age at X-Irradiation and Acute Radiation Mortality in the Adult Male Rat

Jones, D. C.; Osborn, G. K.; Kimeldorf, Donald J.

doi:10.2307/3572620

Cited by 10 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mortality was lower in the youngest mice (1-day and 15-day old), increased in the intermediate age group (30-day old), and decreased again with age in the older age group [20]. Other studies with rats confirmed age-dependent variations in the radiosensitivity of the animals [21]. Our results in minipigs suggest that 6 weeks of age, corresponding to human less than 2 years of age, is not within the time frame when the animals are most sensitive to irradiation.…”

Section: Discussionsupporting

confidence: 49%

Development of Pediatric Model of Hematopoietic Acute Radiation Syndrome (H-Ars) and Countermeasure Testing Using the Göttingen Minipig

Kaur¹,

Vemalapally²,

Severson³

et al. 2017

RadJ

View full text Add to dashboard Cite

Abstract. There is a pressing need to develop animal models as well as treatment appropriate for age-specific radiation injuries. The minipig represents a promising animal model for testing the effects of radiation on the pediatric population. We subjected piglets, age 6 weeks old (corresponding to less than 2 years old in human), to either sham irradiation or to total body irradiation ( 60 Cobalt 0.6 Gy/min) at hematopoietic doses spanning from 1.6 Gy to 2.0 Gy, and determined the dose-survival relationship and course of radiation injury in the presence of minimal supportive care. The LD50/45 was determined to be 1.83 Gy [CI 1.70 -1.91]. The course of hematopoietic acute radiation syndrome (H-ARS) in the piglet model resembled that of humans, with four distinct phases namely, prodromal phase, latent phase, manifest illness phase, and recovery or death. Kinetics of blood cell loss such as sudden lymphopenia, decline in neutrophil counts preceded by initial granulocytosis, erythrocytopenia, and thrombocytopenia with a characteristic shoulder followed by partial recovery mimicked the expected radiationinduced changes. Moribund animals were characterized by anorexia, lethargy, fever or hypothermia, bleeding, and dyspnea. Upon euthanasia, animals displayed dose dependent bone marrow hypoplasia and hemorrhages in several organs. Granulocyte colony stimulating factor (G-CSF), a countermeasure approved for H-ARS in humans and effective in adult minipig, was tested in the piglets. Administration of G-CSF enhanced survival by 37.5% and reduced both duration as well as nadir of neutropenia. In conclusion, the minipig provides a practical and feasible animal model for H-ARS and development of radiation countermeasures for the pediatric population.

show abstract

Section: Discussionsupporting

confidence: 49%

Development of Pediatric Model of Hematopoietic Acute Radiation Syndrome (H-Ars) and Countermeasure Testing Using the Göttingen Minipig

Kaur¹,

Vemalapally²,

Severson³

et al. 2017

RadJ

View full text Add to dashboard Cite

show abstract

“…This could be the consequence of using younger animals (only 200 g b.w.) than in other studies, since they are more radiosensitive than older animals (18). Consequently, survival of 87% of animals can be considered as an excellent radioprotection.…”

Section: Resultsmentioning

confidence: 66%

Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector

et al. 2014

View full text Add to dashboard Cite

AimTo investigate the survival of laboratory rats after irradiation and to study the cellularity of their bone marrow and the multipotential mesenchymal stem cells (BM-MSCs) in groups treated with or without a new thiol-based radioprotector (GM2011)MethodsAnimals were irradiated by a Cobalt gamma source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3 and 7 hours after irradiation. Controls consisted of sham irradiated animals without treatment and animals treated without irradiation. After 30 days post-irradiation, animals were sacrificed and bone marrow cells were prepared from isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to obtain the number of BM-MSCs.ResultsIn the treated group, 87% of animals survived, compared to only 30% in the non-treated irradiated group. Irradiation induced significant changes in the bone marrow of the treated rats (total bone marrow cellularity was reduced by ~ 60% – from 63 to 28 cells ×106/femur and the frequency of the CFU-F per femur by ~ 70% – from 357 to 97), however GL2011 almost completely prevented the suppressive effect observed on day 30 post-irradiation (71 cells ×106/femur and 230 CFU-F/femur).ConclusionAlthough the irradiation dosage was relatively high, GL2011 acted as a very effective new radioprotector. The recovery of the BN-MSCs and their counts support the effectiveness of the studied radioprotector.

show abstract

“…For consistency in results, the routine use of experimental mice at least 3–4 months of age is preferable. On the other hand, irradiated rats were found to be more sensitive at infancy (0–3 weeks) and grew more radiation resistant with age (4–40 weeks), while elderly rats (>65 weeks) were more sensitive than adult rats ( Hursh and Casarett 1956 ; Jones et al 1969 ). A comprehensive review on the impact of age on radiation sensitivity in different species (hamsters, dogs, lamb and sheep) and interrogating endpoints other than survival (hematological end-points, brain injury, and immune pathways) has been published ( Stricklin et al 2018 ).…”

Section: Animal Selectionmentioning

confidence: 99%

Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

DiCarlo

Horta

Rios

et al. 2020

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose: To address confounding issues that have been noted in planning and conducting studies to identify biomarkers of radiation injury, develop animal models to simulate these injuries, and test potential medical countermeasures to mitigate/treat damage caused by radiation exposure. Methods: The authors completed an intensive literature search to address several key areas that should be considered before embarking on studies to assess efficacy of medical countermeasure approaches in mouse models of radiation injury. These considerations include: (1) study variables; (2) animal selection criteria; (3) animal husbandry; (4) medical management; and (5) radiation attributes. Results: It is important to select mouse strains that are capable of responding to the selected radiation exposure (e.g. genetic predispositions might influence radiation sensitivity and proclivity to certain phenotypes of radiation injury), and that also react in a manner similar to humans. Gender, vendor, age, weight, and even seasonal variations are all important factors to consider. In addition, the housing and husbandry of the animals (i.e. feed, environment, handling, time of day of irradiation and animal restraint), as well as the medical management provided (e.g. use of acidified water, antibiotics, routes of administration of drugs, consideration of animal numbers, and euthanasia criteria) should all be addressed. Finally, the radiation exposure itself should be tightly controlled, by ensuring a full understanding and reporting of the radiation source, dose and dose rate, shielding and geometry of exposure, while also providing accurate dosimetry. It is important to understand how all the above factors contribute to the development of radiation dose response curves for a given animal facility with a well-defined murine model. Conclusions: Many potential confounders that could impact the outcomes of studies to assess efficacy of a medical countermeasure for radiation-induced injuries are addressed, and recommendations are made to assist investigators in carrying out research that is robust, reproducible, and accurate.

show abstract

Age at X-Irradiation and Acute Radiation Mortality in the Adult Male Rat

Cited by 10 publications

References 0 publications

Development of Pediatric Model of Hematopoietic Acute Radiation Syndrome (H-Ars) and Countermeasure Testing Using the Göttingen Minipig

Development of Pediatric Model of Hematopoietic Acute Radiation Syndrome (H-Ars) and Countermeasure Testing Using the Göttingen Minipig

Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector

Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

Contact Info

Product

Resources

About