mortality/aging
• about 50% of mice irradiated with a sublethal dose (6.5 Gy) of gamma irradiation die within 15 days while all controls survive beyond 25 days
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• increase in mortality following weekly injections of 150 mg/kg of 5-FU for 3 weeks compared to similarly treated controls
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• decreased lifespan
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hematopoietic system
• by 12 months of age
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• increase in the CD11b+ myeloid fraction
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• decrease in the MPP3 (LSK-CD150-CD48+) cell population
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• increase in cellularity at 2 and 6 months of age
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• increase in percentage and absolute numbers
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• decrease in common lymphoid progenitors and CD19+ lymphoid fraction
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• decreased percentage of B cells at 6 months of age
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• decreased percentage of T cells at 6 months of age
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• increase in peripheral blood cell numbers at 2 4 months of age with a progressive increase in numbers with age
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• increase in percentages and absolute numbers of myeloid-enriched progenitor populations
• myeloid infiltration of femurs by 2 months of age
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• increased percentage of granulocytes at 6 months of age
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• increased percentage of neutrophils at 6 months of age
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• increased percentage of macrophages at 6 months of age
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• increased percentage of monocytes at 6 months of age
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• enlarged follicles at 12 months of age
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• increased accumulation of DNA damage and decreased apoptosis in hematopoietic stem cells
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• in culture cells form larger colonies and a greater number of colonies
• treatment with Nutlin-3, an MDM2 antagonist, inhibits the expansion of hematopoietic stem cells
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homeostasis/metabolism
• at 7 days after irradiation show significantly lower peripheral blood cells counts compared to similarly treated controls
• at 12 days post irradiation hematopoietic stem cell percentages are significantly lower compared to similarly treated controls
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• about 50% of mice irradiated with a sublethal dose (6.5 Gy) of gamma irradiation die within 15 days while all controls survive beyond 25 days
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• increase in mortality following weekly injections of 150 mg/kg of 5-FU for 3 weeks compared to similarly treated controls
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• greater decrease in peripheral blood cell numbers following weekly injections of 150 mg/kg of 5-FU for 3 weeks compared to similarly treated controls
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liver/biliary system
• infiltration of myeloid cells at 12 months of age
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renal/urinary system
• infiltration of myeloid cells at 12 months of age
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skeleton
cellular
• decreased apoptosis of hematopoietic stem cells both in vivo and after short term culture
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• in culture cells form larger colonies and a greater number of colonies
• treatment with Nutlin-3, an MDM2 antagonist, inhibits the expansion of hematopoietic stem cells
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immune system
• by 12 months of age
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• increased percentage of granulocytes at 6 months of age
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• increased percentage of neutrophils at 6 months of age
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• decreased percentage of B cells at 6 months of age
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• decreased percentage of T cells at 6 months of age
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• increased percentage of macrophages at 6 months of age
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• increased percentage of monocytes at 6 months of age
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• enlarged follicles at 12 months of age
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growth/size/body
• by 12 months of age
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