Survival and Oncogenic Transformation of C3H/10T 1/2 Cells after Extended X Irradiation

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Abstract
We performed two independent series of experiments aiming at establishing dose-response curves for lethality or oncogenic transformation in vitro following acute and protracted X-ray doses between 0.25 and 2 Gy. In the first series of experiments, we measured the survival of C3H/10T1.2 CL8 fibroblasts and their transformed counterparts (MCA TCL15) as a function of X-ray dose delivered at 0.49 Gy/min. In addition, 1- and 2-Gy doses were split into four fractions separated by 3-h intervals. The accuracy of survival fraction measurements was about 2%. We found that the dose-response curve at 0.49 Gy/min was a linear function of the dose for both cell lines with a negative slope of 0.171 .+-. 0.007 Gy-1 or 0.160 .+-. 0.003 Gy-1 for 10T1/2 or MCA cells, respectively, indicating a similar initial radiosensitivity of normal and transformed 10T1/2 cells. Dose fractionation resulted in a significant increase of the survival, relative to that measured when x-ray dose was delivered in a single fraction. The enhancement of survival was not, however, significantly different for 10T1/2 and MCA cells, indicating similar cellular repair abilities. In the second series of experiments, we measured oncogenic transformation in vitro (along with the survival) of C3H/10T1/2 cells, using a constant exposure time technique in which the dose rate was proportional to the total dose so that the repair time was equal at all dose levels. The dose-response curves for oncogenic transformation in the low-dose range between 0.25 and 2 Gy were consistent with a linear response with a positive slope 2.50 .+-. 0.11 .times. 10-4, 1.50 .+-. 0.03 .times. 10-4, or 0.87 .+-. 0.05 .times. 10-4 Gy-1, for acute, 1-h, or 3-h protracted exposures, respectively. Hence, relative to the acute irradiation, the 1- or 3-h protraction of the X-ray dose reduced the slopes by 0.60 .+-. 0.03 or 0.35 .+-. 0.03, respectively. These results indicate that in the dose range between 0.25 to 2 Gy, the dose-response curves for survival or oncogenic transformation were linear and can be modified by the temporal distribution of the X-ray dose.