Establishing Pediatric Mouse Models of the Hematopoietic Acute Radiation Syndrome and the Delayed Effects of Acute Radiation Exposure
| Autor: | Hailin Feng, P. Artur Plett, Hui Lin Chua, Catherine Booth, Gregory Tudor, Carol H. Sampson, Alexa Fisher, Rajendran Sellamuthu, Andrea M. Patterson, Thomas J. MacVittie, Barry P. Katz, Christie M. Orschell, Steven J. Miller, Sasidhar Vemula |
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| Rok vydání: | 2020 |
| Předmět: |
Filgrastim
Hematopoietic System Biophysics Physiology Pediatrics Radiation Tolerance 030218 nuclear medicine & medical imaging Polyethylene Glycols 03 medical and health sciences Mice 0302 clinical medicine Radioresistance medicine Animals Humans Radiology Nuclear Medicine and imaging Increased blood urea nitrogen Acute radiation exposure Radiation business.industry Acute Radiation Syndrome Haematopoiesis Disease Models Animal 030220 oncology & carcinogenesis medicine.symptom business Weight gain Pegfilgrastim Radiation response Whole-Body Irradiation medicine.drug |
| Zdroj: | Radiation research. 195(4) |
| ISSN: | 1938-5404 |
| Popis: | Medical countermeasures (MCMs) for hematopoietic acute radiation syndrome (H-ARS) should be evaluated in well-characterized animal models, with consideration of at-risk populations such as pediatrics. We have developed pediatric mouse models of H-ARS and delayed effects of acute radiation exposure (DEARE) for efficacy testing of MCMs against radiation. Male and female C57BL/6J mice aged 3, 4, 5, 6, 7 and 8 weeks old (±1 day) were characterized for baseline hematopoietic and gastrointestinal parameters, radiation response, efficacy of a known MCM, and DEARE at six and 12 months after total-body irradiation (TBI). Weanlings (age 3 weeks) were the most radiosensitive age group with an estimated LD50/30 of 712 cGy, while mice aged 4 to 8 weeks were more radioresistant with an estimated LD50/30 of 767-787 cGy. Female weanlings were more radiosensitive than males at 3 and 4 weeks old but became significantly more radioresistant after the pubertal age of 5 weeks. The most dramatic increase in body weight, RBC counts and intestinal circumference length occurred from 3 to 5 weeks of age. The established radiomitigator Neulasta® (pegfilgrastim) significantly increased 30-day survival in all age groups, validating these models for MCM efficacy testing. Analyses of DEARE among pediatric survivors revealed depressed weight gain in males six months post-TBI, and increased blood urea nitrogen at 12 months post-TBI which was more severe in females. Hematopoietic DEARE at six months post-TBI appeared to be less severe in survivors from the 3- and 4-week-old groups but was equally severe in all age groups by 12 months of age. Similar to our other acute radiation mouse models, there was no appreciable effect of Neulasta used as an H-ARS MCM on the severity of DEARE. In summary, these data characterize a pediatric mouse model useful for assessing the efficacy of MCMs against ARS and DEARE in children. |
| Databáze: | OpenAIRE |
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