Wangenheim K H, Peterson H P, Hübner G E, Feinendegen L E
Ann N Y Acad Sci. 1985;459:221-31. doi: 10.1111/j.1749-6632.1985.tb20829.x.
For the measurement of long-term residual radiation effect in the murine hematopoietic system a test system was developed that quantifies the proliferation ability of progeny of spleen repopulating cells by the proliferation factor (PF). The PF expresses the ratios of 125IUdR incorporation in the recipient spleens at days 3 and 5 following cell transfusion, thus measuring the relative increase in number of proliferating cells. Following 500 rad whole-body gamma irradiation, PF recovered up to 6 months and remained thereafter, on the average, at 80% of control. Recovery of the number of 7-day CFU-S was similar to recovery of PF. Various studies were aimed at elucidating the reasons for reduction in PF. Loss of incorporated 125IUdR activity from spleens between days 3 and 5 after cell transfusion indicates loss of mature labeled cells. When the doubling time of proliferating cells of CFU-S progeny (td) is corrected for cell loss, td for control bone marrow approaches mitotic cycle time in normal bone marrow as was found elsewhere. Following 500 rad, both cell loss and td were initially increased and recovered in parallel with PF and number of CFU-S. Reduction of PF could be brought about by radiation-induced increase in transient CFU-S with the consequence of increased loss of mature cells between days 3 and 5. This possibility was excluded by the observation that 1 year after 500 rad the number of colonies per spleen did not decrease from day 7 to day 12 after cell transfusion, as was expected from a higher proportion of transient CFU-S, but increased more than in the controls. Measurement of these 12-day colonies showed a significantly reduced size. Average progeny from irradiated CFU-S, apparently, grow more slowly. It is concluded that sublethal injury resides in stem cells, increases mitotic cycle time, and causes precocious loss of cells from spleens probably by enhanced differentiation and maturation due to interference with endocellular control of cell proliferation and differentiation. Probably the observed recovery proceeds via replacement of injured stem cells by less injured or normal stem cells.
为了测量小鼠造血系统中的长期残余辐射效应，开发了一种测试系统，该系统通过增殖因子（PF）对脾再填充细胞后代的增殖能力进行量化。PF表示细胞输注后第3天和第5天受体脾脏中¹²⁵IUdR掺入率的比值，从而测量增殖细胞数量的相对增加。在接受500拉德全身γ射线照射后，PF恢复长达6个月，此后平均维持在对照的80%。7天集落形成单位脾集落（CFU-S）数量的恢复与PF的恢复相似。多项研究旨在阐明PF降低的原因。细胞输注后第3天至第5天脾脏中¹²⁵IUdR活性掺入的丧失表明成熟标记细胞的丧失。当校正CFU-S后代增殖细胞的倍增时间（td）以考虑细胞损失时，对照骨髓的td接近正常骨髓中的有丝分裂周期时间，这与其他地方的发现一致。接受500拉德照射后，细胞损失和td最初均增加，并与PF和CFU-S数量平行恢复。PF降低可能是由于辐射诱导瞬时CFU-S增加，导致第3天至第5天成熟细胞损失增加。这一可能性被以下观察结果排除：在接受500拉德照射1年后，细胞输注后第7天至第12天每个脾脏的集落数量并未如预期的那样因瞬时CFU-S比例较高而减少，反而比对照组增加得更多。对这些12天集落的测量显示其大小显著减小。显然，受照射CFU-S的平均后代生长更缓慢。结论是，亚致死损伤存在于干细胞中，增加有丝分裂周期时间，并可能由于干扰细胞增殖和分化的细胞内控制而导致脾脏细胞过早丧失，可能是通过增强分化和成熟。观察到的恢复可能是通过损伤较轻或正常的干细胞替代受损干细胞来实现的。
