Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97851
Title:
Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells.
Authors:
Yang, F T; Lord, Brian I; Hendry, Jolyon H
Abstract:
Hemopoiesis is the product of two components: the hemopoietic tissue and the regulatory stromal microenvironment in which it resides. Plutonium-239, incorporated during fetal development, is known to cause deficient hemopoiesis. A predetermined equivalent gamma-ray dose has now been used in combination with cross-transplantation experiments to separate these two components and define where the damage arises. It was confirmed that 1.8 Gy gamma irradiation at midterm gestation caused a 40% reduction in the hemopoietic stem (spleen colony-forming) cell population of their offspring which persisted to at least 24 weeks of age. Spleen colony formation after sublethal doses of gamma rays reflected this reduced complement of endogenous stem cells. The regulatory hemopoietic microenvironment, measured as fibroblastoid colony-forming cells, was similarly depleted. Normal growth of the CFU-S population after transplantation into standard recipients showed that the quality of the stem cell population in the offspring of irradiated mothers was not affected. By contrast, when used as recipients of a bone marrow transplant from either normal or irradiated offspring, the offspring of irradiated mothers were unable to support normal growth: there was a twofold difference in the number of CFU-S per femur for at least 100 days after transplantation. There were 70% fewer CFU-F in the femur 1 month after bone marrow transplantation when the offspring of irradiated mothers were used as transplant recipients compared to when normal offspring were used. This not only confirmed their reduced capacity to host normal stem cells but also indicated that CFU-F in the transplant were unable to compensate for the poor microenvironment in the irradiated offspring hosts. It is concluded that irradiation at midterm gestation damages the developing regulatory microenvironment but not the hemopoietic stem cell population that it hosts.
Affiliation:
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, England.
Citation:
Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells. 1995, 141 (3):309-13 Radiat. Res.
Journal:
Radiation Research
Issue Date:
Mar-1995
URI:
http://hdl.handle.net/10541/97851
PubMed ID:
7871158
Type:
Article
Language:
en
ISSN:
0033-7587
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorYang, F Ten
dc.contributor.authorLord, Brian Ien
dc.contributor.authorHendry, Jolyon Hen
dc.date.accessioned2010-05-04T13:05:24Z-
dc.date.available2010-05-04T13:05:24Z-
dc.date.issued1995-03-
dc.identifier.citationGamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells. 1995, 141 (3):309-13 Radiat. Res.en
dc.identifier.issn0033-7587-
dc.identifier.pmid7871158-
dc.identifier.urihttp://hdl.handle.net/10541/97851-
dc.description.abstractHemopoiesis is the product of two components: the hemopoietic tissue and the regulatory stromal microenvironment in which it resides. Plutonium-239, incorporated during fetal development, is known to cause deficient hemopoiesis. A predetermined equivalent gamma-ray dose has now been used in combination with cross-transplantation experiments to separate these two components and define where the damage arises. It was confirmed that 1.8 Gy gamma irradiation at midterm gestation caused a 40% reduction in the hemopoietic stem (spleen colony-forming) cell population of their offspring which persisted to at least 24 weeks of age. Spleen colony formation after sublethal doses of gamma rays reflected this reduced complement of endogenous stem cells. The regulatory hemopoietic microenvironment, measured as fibroblastoid colony-forming cells, was similarly depleted. Normal growth of the CFU-S population after transplantation into standard recipients showed that the quality of the stem cell population in the offspring of irradiated mothers was not affected. By contrast, when used as recipients of a bone marrow transplant from either normal or irradiated offspring, the offspring of irradiated mothers were unable to support normal growth: there was a twofold difference in the number of CFU-S per femur for at least 100 days after transplantation. There were 70% fewer CFU-F in the femur 1 month after bone marrow transplantation when the offspring of irradiated mothers were used as transplant recipients compared to when normal offspring were used. This not only confirmed their reduced capacity to host normal stem cells but also indicated that CFU-F in the transplant were unable to compensate for the poor microenvironment in the irradiated offspring hosts. It is concluded that irradiation at midterm gestation damages the developing regulatory microenvironment but not the hemopoietic stem cell population that it hosts.en
dc.language.isoenen
dc.subjectFoetusen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshBone Marrow-
dc.subject.meshBone Marrow Cells-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshFemale-
dc.subject.meshFetus-
dc.subject.meshGamma Rays-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Inbred DBA-
dc.subject.meshSpleen-
dc.subject.meshStromal Cells-
dc.titleGamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, England.en
dc.identifier.journalRadiation Researchen
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