DOSE-RATE EFFECTS BETWEEN 0.3 AND 30 GY H IN A NORMAL AND A MALIGNANTHUMAN CELL-LINE/

Purpose: This study used continuous ''intermediate'' dose rate irradia tion (0.3-30 Gy/h) to compare the capacity for and repair of sublethal radiation damage in different cell lines growing in tissue culture. M ethods and Materials: Two human cell lines were studied; one was deriv ed from normal human fibroblasts (AG1522) and the other from a squamou s cell carcinoma of the uterine cervix (HTB-35). Dose-response curves for clonogenic survival were determined following irradiation of plate au-phase cultures at five different dose rates: 22.6, 6.12, 3.65, 1.04 , and 0.38 Gy/h. Subculture following irradiation was delayed for 8-24 h to allow for the full repair of ''potentially lethal damage.'' Resu lts: A significant dose-rate effect was seen in both cell lines. For i rradiation at the highest dose rate, survival at 2 Gy (SF2) and the al pha/beta ratio were similar for the two cell lines (approximately 0.7 and 8.0 Gy, respectively) but the half-time of repair of sublethal dam age was estimated to be approximately five times longer in the normal human fibroblast line (154 min) than in the carcinoma (31 min) cell li ne. Conclusion: These results indicate that measuring the dose-rate ef fect between 0.3 and 30 Gy/h is a useful way to identify and quantify differences in sublethal damage repair between cell lines. To the exte nt that in vitro and in vivo repair parameters are similar, and that r epresentative tumor biopsy specimens can be examined in this way, this approach may provide a prospective way of determining the dose rate ( brachytherapy) or fractionation schedule that will optimize the therap eutic ratio.