Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells
- Paterson Institute for Cancer Research, Manchester (United Kingdom)
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 in mice, 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. 12 refs., 1 fig., 4 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 81198
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 141; ISSN 0033-7587; ISSN RAREAE
- Country of Publication:
- United States
- Language:
- English
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