Establishment of a mouse model of 70% lethal dose by total-body irradiation

Ryu, Seunghyun; Park, Jong‐Hyung; Jeong, Eui‐Suk; Choi, Seri; Ham, Seung‐Hoon; Park, Jin‐Il; Jeon, Hee‐Yeon; Kim, Junyoung; Yoo, Ran-Ji; Lee, Yongjin; Woo, Sang-Keun; Choi, Yang‐Kyu

doi:10.5625/lar.2016.32.2.116

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…For example, immunological responses to radiation and radiation combined injury were recently studied in CD-1 mice (an outbred strain from Charles River), since the genetic composition of an outbred strain may be more comparable to the human response (Tajima et al 2013). In addition, a study done comparing ICR (outbred) and C57BL/6N mice found that the radiation-induced mortality seen for the inbred mice was generally higher than what was observed for the outbred strain (Ryu et al 2016).…”

Section: Mouse Strainmentioning

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

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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.

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Section: Mouse Strainmentioning

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

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“…United Nations Scientific Committee on the Effects of Atomic Radiation classifies LDR as any radiation dose below 100 mGy [29]. High dose radiation varies significantly ranging between 2000 mGy and 15 000 mGy [30][31][32][33]. High doses are usually accumulated during multiple exposures rather than a one-time whole-body exposure.…”

Section: Introductionmentioning

confidence: 99%

Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue

et al. 2020

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Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern. However, the impact of low dose and sub-lethal dose radiation (SLDR) exposures remain contentious, particularly in pregnant women who represent a vulnerable group. The fetal programming hypothesis states that an adverse in utero environment or stress during development of an embryo or fetus can result in permanent physiologic changes often resulting in progressive metabolic dysfunction with age. To assess changes in gene expression profiles of glucose/insulin signaling and lipid metabolism caused by radiation exposure in utero, pregnant C57Bl/6J mice were irradiated using a dose response ranging from low dose to SLDR and compared to a Sham-irradiated group. mRNA expression analysis in 16 week old offspring (n = 84) revealed that genes involved in metabolic function including glucose metabolism, insulin signaling and lipid metabolism were unaffected by prenatal radiation exposures up to 300 mGy. However, female offspring of dams exposed to 1000 mGy had upregulated expression of genes contributing to insulin resistance and gluconeogenesis. In a second cohort of mice, the effects of SLDR on fetal programming of hepatic SOCS3 and PEPCK protein expression were assessed. 4 month old female offspring of dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic expression of proteins involved in glucose metabolism and 3) increased 18 F-fluorodeoxyglucose (FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET) (n = 25). The results of this study indicate that prenatal radiation exposure does not affect metabolic function up to 300 mGy and 1000 mGy may be a threshold dose for sex-specific alterations in glucose uptake and hepatic gene and protein expression of SOCS3, PEPCK, PPARGC1A and PPARGC1B. These findings suggest that SLDR doses

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“…Several conventional radiobiology studies have shown the loss of body weight along with the loss in most of the organ weight during the first initial days post-irradiation in non-lethal to sub-lethal cases 48 – 51 . However, our result shows the damages only to hematopoietic system organ due to the local radiation exposure to bone marrow cells.…”

Section: Discussionmentioning

confidence: 99%

“…This result corroborated with the cell counts of spleen and thymus which shows continuous loss in cell number in this group upto 10th day post irradiation and beyond that restoration process started with full recovery at 30th day post irradiation. Several conventional radiobiology studies have shown the loss of body weight along with the loss in most of the organ weight during the first initial days post-irradiation in non-lethal to sub-lethal cases [48][49][50][51] . However, our result shows the damages only to hematopoietic system organ due to the local radiation exposure to bone marrow cells.…”

Section: Discussionmentioning

confidence: 99%

Development of hematopoietic syndrome mice model for localized radiation exposure

Yashavarddhan

Sharma

Chaudhary

et al. 2021

Sci Rep

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Current models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain ‘A’ male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1β, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1β levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.

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Establishment of a mouse model of 70% lethal dose by total-body irradiation

Cited by 10 publications

References 23 publications

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

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

Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue

Development of hematopoietic syndrome mice model for localized radiation exposure

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