Lifelong Residual bone Marrow Damage in Murine Survivors of the Hematopoietic Acute Radiation Syndrome (H-ARS): A Compilation of Studies Comprising the Indiana University Experience
Abstract
Accurate analyses of the delayed effects of acute radiation exposure in survivors of the hematopoietic acute radiation syndrome are hampered by low numbers of mice for examination due to high lethality from the acute syndrome, increased morbidity and mortality in survivors, high cost of husbandry for long-term studies, biological variability, and inconsistencies of models from different laboratories complicating meta-analyses. To address this, a compilation of 38 similar hematopoietic acute radiation syndrome studies conducted over a 7-y period in the authors' laboratory, comprising more than 1,500 irradiated young adult C57BL/6 mice and almost 600 day-30 survivors, was assessed for hematopoietic delayed effects of acute radiation exposure at various times up to 30 mo of age. Significant loss of long-term repopulating potential of phenotypically defined primitive hematopoietic stem cells was documented in hematopoietic acute radiation syndrome survivors, as well as significant decreases in all hematopoietic lineages in peripheral blood, prominent myeloid skew, significantly decreased bone marrow cellularity, and numbers of lineage-negative Sca-1+ cKit+ CD150+ cells (KSL CD150+; the phenotype known to be enriched for hematopoiet...Continue Reading
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Non-clinical radiation biology and pharmacology models: appraisal of state-of-the-art and innovation
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