Recovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates.

2.50
Hdl Handle:
http://hdl.handle.net/10541/104682
Title:
Recovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates.
Authors:
Bierkens, J G; Hendry, Jolyon H; Testa, Nydia G
Abstract:
Injury inflicted upon the bone marrow stroma following whole-body irradiation and its repair over a 1-year period has been assessed in murine long-term bone marrow cultures established at increasing time intervals after irradiation. Different doses at different dose rates (10 Gy at 0.05 cGy/min, 4.5 Gy and 10 Gy at 1.6 cGy/min, and 4 x 4.5 Gy [3 weeks between doses] at 60 cGy/min) were chosen so as to maximize differences in effect in the stroma. The cellularity of the adherent layer in long-term cultures established 1 month after irradiation was reduced by 40%-90% depending on the dose and dose rate. Simultaneous with the poor ability of the marrow to form adherent layers, the cumulative spleen colony-forming unit (CFU-S) and granulocyte-macrophage colony-forming cell (GM-CFC) production over a 7-week period was reduced to 0% and 30% of control cultures, respectively. The slow recovery of the adherent layer was paralleled by an increase in the numbers of CFU-S and GM-CFC in the supernatant. Cultures established from repeatedly irradiated mice performed poorly over the entire 1-year period. Whereas the regeneration of the stroma was near complete 1 year after irradiation, the CFU-S and GM-CFC levels reached only between 50% and 80% of control cultures, respectively. Also, the concentration of CFU-S and GM-CFC in the supernatant remained persistently lower in cultures established from irradiated mice as compared to control cultures. The levels of sulfated glycosaminoglycans, which have been implicated in the establishment of the functional integrity of the microenvironment, were not reduced in the adherent layers at any time after irradiation. These results indicate that the regeneration of the stroma is accompanied by an incomplete recovery of active hemopoiesis in vitro. However, no evidence was found for persistent functional defects in the stroma after irradiation, using the present endpoints.
Affiliation:
Cancer Research Campaign Department of Radiobiology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Citation:
Recovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates. 1991, 19 (2):81-6 Exp. Hematol.
Journal:
Experimental Hematology
Issue Date:
Feb-1991
URI:
http://hdl.handle.net/10541/104682
PubMed ID:
1991498
Type:
Article
Language:
en
ISSN:
0301-472X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBierkens, J Gen
dc.contributor.authorHendry, Jolyon Hen
dc.contributor.authorTesta, Nydia Gen
dc.date.accessioned2010-06-11T10:45:00Z-
dc.date.available2010-06-11T10:45:00Z-
dc.date.issued1991-02-
dc.identifier.citationRecovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates. 1991, 19 (2):81-6 Exp. Hematol.en
dc.identifier.issn0301-472X-
dc.identifier.pmid1991498-
dc.identifier.urihttp://hdl.handle.net/10541/104682-
dc.description.abstractInjury inflicted upon the bone marrow stroma following whole-body irradiation and its repair over a 1-year period has been assessed in murine long-term bone marrow cultures established at increasing time intervals after irradiation. Different doses at different dose rates (10 Gy at 0.05 cGy/min, 4.5 Gy and 10 Gy at 1.6 cGy/min, and 4 x 4.5 Gy [3 weeks between doses] at 60 cGy/min) were chosen so as to maximize differences in effect in the stroma. The cellularity of the adherent layer in long-term cultures established 1 month after irradiation was reduced by 40%-90% depending on the dose and dose rate. Simultaneous with the poor ability of the marrow to form adherent layers, the cumulative spleen colony-forming unit (CFU-S) and granulocyte-macrophage colony-forming cell (GM-CFC) production over a 7-week period was reduced to 0% and 30% of control cultures, respectively. The slow recovery of the adherent layer was paralleled by an increase in the numbers of CFU-S and GM-CFC in the supernatant. Cultures established from repeatedly irradiated mice performed poorly over the entire 1-year period. Whereas the regeneration of the stroma was near complete 1 year after irradiation, the CFU-S and GM-CFC levels reached only between 50% and 80% of control cultures, respectively. Also, the concentration of CFU-S and GM-CFC in the supernatant remained persistently lower in cultures established from irradiated mice as compared to control cultures. The levels of sulfated glycosaminoglycans, which have been implicated in the establishment of the functional integrity of the microenvironment, were not reduced in the adherent layers at any time after irradiation. These results indicate that the regeneration of the stroma is accompanied by an incomplete recovery of active hemopoiesis in vitro. However, no evidence was found for persistent functional defects in the stroma after irradiation, using the present endpoints.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBone Marrow-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshDose-Response Relationship, Radiation-
dc.subject.meshFemale-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshGranulocytes-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshMacrophages-
dc.subject.meshMice-
dc.subject.meshTime Factors-
dc.subject.meshWhole-Body Irradiation-
dc.titleRecovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Radiobiology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalExperimental Hematologyen
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