Continuous One Year Oral Administration of the Radiation Mitigator, MMS350, after Total-Body Irradiation, Restores Bone Marrow Stromal Cell Proliferative Capacity and Reduces Senescence in Fanconi Anemia (Fanca
| Autor: | Darcy Franicola, Donna Shields, Joel S. Greenberger, Michael W. Epperly, Renee Fisher, Wen Hou, Xichen Zhang, Aranee Sivananthan, Peter Wipf |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Senescence Male congenital hereditary and neonatal diseases and abnormalities Biophysics Administration Oral Radiation-Protective Agents Article 03 medical and health sciences Mice 0302 clinical medicine Oral administration Fanconi anemia Ethers Cyclic hemic and lymphatic diseases medicine Tumor Microenvironment Animals Radiology Nuclear Medicine and imaging Cellular Senescence Cell Proliferation Mice Knockout Radiation Fanconi Anemia Complementation Group A Protein business.industry Proliferative capacity nutritional and metabolic diseases Mesenchymal Stem Cells Total body irradiation medicine.disease FANCA In vitro 030104 developmental biology Fanconi Anemia Cell culture 030220 oncology & carcinogenesis Sulfoxides Cancer research Female business Whole-Body Irradiation |
| Zdroj: | Radiation research. 191(2) |
| ISSN: | 1938-5404 |
| Popis: | We quantitated age-related accumulation of senescent cells in irradiated Fanconi anemia (FA) (Fanca(−/−)) mouse cell lines in vitro and monitored the effect of continuous administration (via drinking water) of the water-soluble radiation mitigator, MMS350, on tissues in vivo over one year after 7.5 Gy total-body irradiation (TBI). Irradiated Fanca(−/−) mouse bone marrow stromal cell lines showed increased numbers of beta-galactosidase- and p21-positive senescent cells compared to Fanca(+/+) cell lines, which was reduced by MMS350. One week after 7.5 Gy TBI, Fanca(−/−) mice showed increased numbers of senescent cells in spleen compared to Fanca(+/+) controls, decreased bone marrow cellularity, failure of explanted bone marrow to proliferate in vitro to form a hematopoietic microenvironment and no detectable single stromal cell cloning capacity. There was no detectable amelioration by MMS350 administration at one week. In contrast, one year post-TBI, Fanca(−/−) mice demonstrated fewer senescent cells in brain and spleen compared to Fanca(+/+) controls. While Fanca(−/−) mouse bone marrow stromal cells explanted one year post-TBI still failed to proliferate in vitro, continuous oral administration of 400 μM, MMS350 in drinking water restored explanted stromal cell proliferation. The data indicate that continuous administration of MMS350 modulated several properties of TBI-accelerated aging in Fanca(−/−) mice as well as control mice, and support further study of MMS350 as a modulator of radiation late effects. |
| Databáze: | OpenAIRE |
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