The relationships between DNA damage and the survival of murine bone marrow cells irradiated in situ were examined. Cell survival was assayed by the ability of bone marrow cells from irradiated mice to form colonies in vitro (CFU-C). DNA double-strand breaks (DSBs) were measured by neutral (nondenaturing) filter elution and pulsed-field gel electrophoresis (PFGE). Double-strand breaks were measured in the proliferating bone marrow cells, identified by injecting the mice with [3 H] dThd at various times before γ irradiation, as a model of the behavior of the radiosensitive target cells. To assess how the DNA lesions measured using these techniques correlated with cell killing, the effect of the radioprotective agent WR-2721 on the induction of DSBs in proliferating bone marrow cells was compared with its effect on CFU-C survival. WR-2721 protected against the killing of both granulocyte-macrophage and erythroid burst-forming CFU-C by a factor of about 2. In contrast, little (1.2-fold) protection was observed in the PFGE assay at radiation doses between 5 and 20 Gy. Similarly, at the lowest dose studied (5 Gy) there was little protection against DSBs as measured by neutral elution; only after doses of between 10 and 30 Gy was significant protection observed. Thus the previously reported predictive relationship between DSBs and cell survival in vitro does not appear to extend directly to murine bone marrow cells irradiated in vivo.

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