Grande T, Varas F, Bueren J A
Unidad de Biología Molecular y Celular, CIEMAT, Madrid, Spain.
Exp Hematol. 2000 Jan;28(1):87-95. doi: 10.1016/s0301-472x(99)00128-9.
The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development.
Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months postirradiation, the effects generated within the different compartments of repopulating cells (RCs) were evaluated by determining, in a BM competition assay, the contribution of the irradiated precursors to the lymphohematopoiesis of recipients at different times posttransplantation (3, 9, and 15 months).
The irradiation of 4-day-old embryos with either 1 or 3 Gy did not produce residual repopulation or differentiation effects within the different RCs assayed. However, significant impairments in RC functionality were observed in mice irradiated on the 17th day postconception or at the 12th week of age. Whereas irradiation of these animals with 1 Gy did not impair the long-term functionality of the very primitive 15-month-old RCs, irradiation with 3 Gy generated sustained impairment in all tested types of hematopoietic progenitors and RCs. Moreover, repopulation data derived from the analysis of recipient BM and thymus strongly suggested that the observed effects were produced within the multipotent pool of lymphohematopoietic RCs.
Our data show the generation of long-term effects in the multipotent RCs of mice irradiated at fetal and adult stages of growth and reveals the normal functionality of the RCs from animals irradiated during the early stages of embryonic development.
本研究旨在评估在胚胎发育和成年发育阶段接受辐照的小鼠骨髓(BM)的再增殖特性。
对4日龄胚胎、17日龄胎儿和12周龄小鼠进行1或3 Gy的X射线辐照。在辐照后3个月和9个月,通过在骨髓竞争试验中测定辐照前体细胞对移植后不同时间(3、9和15个月)受体淋巴细胞生成的贡献,评估再增殖细胞(RCs)不同区室产生的影响。
用1或3 Gy辐照4日龄胚胎,在所检测的不同RCs中未产生残留的再增殖或分化效应。然而,在受孕后第17天或12周龄接受辐照的小鼠中,观察到RC功能有显著损害。虽然用1 Gy辐照这些动物不会损害非常原始的15月龄RCs的长期功能,但用3 Gy辐照会使所有测试类型的造血祖细胞和RCs产生持续损害。此外,对受体骨髓和胸腺分析得出的再增殖数据强烈表明,观察到的效应是在淋巴细胞生成RCs的多能池中产生的。
我们的数据显示,在胎儿期和成年期生长阶段接受辐照的小鼠多能RCs中产生了长期效应,并揭示了在胚胎发育早期接受辐照的动物的RCs的正常功能。