RELATIONSHIPS BETWEEN DNA-DAMAGE AND THE SURVIVAL OF MURINE BONE-MARROW CELLS IRRADIATED IN-SITU

The relationships between DNA damage and the survival of murine bone m arrow cells irradiated in situ were examined. Cell survival was assaye d by the ability of bone marrow cells from irradiated mice to form col onies in vitro (CFU-C). DNA double-strand breaks (DSBs) were measured by neutral (nondenaturing) filter elution and pulsed-held gel electrop horesis (PFGE). Double-strand breaks were measured in the proliferatin g bone marrow cells, identified by injecting the mice with [H-3]dThd a t various times before gamma irradiation, as a model of the behavior o f the radiosensitive target cells. To assess how the DNA lesions measu red using these techniques correlated with cell killing, the effect of the radioprotective agent WR-2721 on the induction of DSBs in prolife rating bone marrow cells was compared with its effect on CFU-C surviva l. WR-2721 protected against the killing of both granulocyte-macrophag e and erythroid burst-forming CFU-C by a factor of about 2. In contras t, little (1.2-fold) protection was observed in the PFGE assay at radi ation doses between 5 and 20 Gy. Similarly, at the lowest dose studied (5 Gy) there was little protection against DSBs as measured by neutra l elution; only after doses of between 10 and 30 Gy was significant pr otection observed. Thus the previously reported predictive relationshi p between DSBs and cell survival in vitro does not appear to extend di rectly to murine bone marrow cells irradiated in vivo.