Repair of DNA single- and double-strand breaks in proliferating and quiescent murine tumor cells.
We evaluated the relationship between the repair of DNA single- and double-strand breaks and cellular radiosensitivity in proliferating vs. quiescent cells of the mouse mammary tumor lines 66 and 67 in vitro, using the technique of filter elution at pH 12.2, pH 7.2 and pH 9.6. In these lines, quiescent (Q; unfed plateau-phase) cells are more radiosensitive than are proliferating (P) cells. At doses of 4-6 Gy, both 66 and 67 Q cells repair single-strand breaks (ssb) with kinetics similar to those of P cells. However, repair of ssb was slightly retarded in Q cells at a higher dose (10 Gy) than at the lower doses. In contrast, repair of ssb in P cells was dose-independent, at least for doses up to 10 Gy. The rate of repair of DNA double-strand breaks (dsb), measured at pH 7.2, was dose-independent in P and Q cells of both lines. The repair kinetics were biphasic, with an initial half-time less than 15 min, and the early phase was similar in all cell groups. The half-time for repair in the slow phase ranged from about 2 to greater than 20 h. The fraction of damage repaired by the slow phase was relatively high in all cell groups (40-70 per cent). In line 66, P cells repaired a higher percentage of dsb by 2 h postirradiation than did Q cells. The opposite was observed in line 67: Q cells repaired more dsb in 2 h than did P cells. The survival of 66 St4 cells (Q cultures which have been refed with complete medium and incubated 4 h) was significantly greater than that of 66 Q; nevertheless St4 cells repaired both ssb and dsb at rates similar to those of Q cells. Therefore, survival does not necessarily correlate with the rates of either ssb or dsb repair among these cell lines in different growth states.
Sweigert
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Department of Radiology, University of Utah Health Sciences Center, Salt Lake City 84132.
Eguchi-Kasai
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Warters
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Dethlefsen
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D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000378:metabolism / Q000528:radiation effects*; D004277:DNA, Single-Stranded / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D051379:Mice; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded