Someras-transformed cells have increased radiosensitivity and decreased repair of sublethal radiation damage

Abstract

We examined the effect of 60Co irradiation on the clonogenic survival of rat NRK cells, NRK cells carrying a temperature-sensitive viral K-ras oncogene (tsK-NRK), mouse NIH 3T3 cells, and NIH 3T3 cells transformed with the human bladder cancer (T24) H-ras oncogene (PAP2). We tested the hypothesis that ras oncogene expression renders cells more resistant to radiation, but found in both systems that ras-transformed cells were more, not less, sensitive to radiation. We also found indications of altered repair of sublethal radiation damage. PAP2 cells were more sensitive to radiation than NIH 3T3 cells. Increased sensitivity was reflected in a decreased shoulder region of the survival curve with little effect on its slope (D0). TsK-NRK cells were also slightly more sensitive to radiation than NRK and exhibited decreased repair of sublethal damage at both the permissive and nonpermissive temperatures. Thus, we found that expression of ras oncogenes is not always associated with increased radiation resistance. In summary, our results suggest that (1) ras oncogene expression in some cells may be associated with increased, rather than decreased, radiation sensitivity, and (2) ras oncogene expression may alter the shoulder region of the dose response curve, suggesting changes in the repair of sublethal radiation damage.