Effects of hyperthermia on the repair of radiation-induced DNA single- and double-strand breaks in DNA double-strand break repair-deficient and repair-proficient cell lines.
The effect of heat on the induction and repair of DNA single (ssb) and double (dsb) strand breaks was studied in irradiated exponentially growing or plateau-phase CHO cells and their DNA dsb repair-deficient, radiation-sensitive counterpart, the xrs-5 cells. Induction and repair of DNA ssb was measured by the alkaline unwinding technique, whereas induction and repair of DNA dsb was measured by the non-unwinding filter elution technique. The results indicated that pre-exposure of cells to heat (45 x 5 degrees C) for 8-30 min did not affect the induction of DNA ssb or DNA dsb per Gy and dalton of DNA in CHO or xrs-5 cells, tested either in the exponential or in the plateau-phase of growth. On the other hand, pre-exposure to heat inhibited DNA repair processes and increased the fraction of unrepaired radiation-induced damage measured 2 h after irradiation. Repair of DNA dsb was more heat-sensitive than repair of DNA ssb in both cell lines. Repair of radiation-induced ssb or dsb was inhibited in xrs-5 cells to a larger extent than in CHO cells after a similar exposure to heat. These results complement those previously reported on heat-induced radiosensitization in these cell lines, and suggest that the reduction in heat-induced radiosensitization observed in xrs-5 cells is largely due to their deficiency in repairing DNA dsb, rather than to a reduction in the ability of heat to inhibit DNA repair processes in general. The data presented here provide further support to the hypothesis that DNA dsb repair proficiency is a prerequisite for heat-induced radiosensitization.
Thomas Jefferson University, Department of Radiation Oncology, Philadelphia, PA.
G
G
Iliakis
R
R
Seaner
R
R
Okayasu
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004277:DNA, Single-Stranded / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006358:Hot Temperature; D007700:Kinetics; D009154:Mutation; D011836:Radiation Tolerance
D004277:DNA, Single-Stranded