Equivalence of pulsed-dose-rate to low-dose-rate irradiation in tumor and normal cell lines

To determine whether different fractionation schemes could simulate low-dos e-rate irradiation, ovarian cells of the carcinoma cell lines A2780s (radio sensitive) and A2780cp (radioresistant) and AG1522 normal human fibroblasts were irradiated in vitro using different fraction sizes and intervals betw een fractions with an overall average dose rate of 0.53 Gy/h. For the resis tant cell line, the three fractionation schemes, 0.53 Gy given every hour, 1.1 Gy every 2 h, and 1.6 Gy every 3 h, were equivalent to low dose rate (0 .53 Gy/h). Two larger fraction sizes, 2.1 Gy every 4 h and 3.2 Gy every 6 h , resulted in lower survival than that after low-dose-rate irradiation for the resistant cell line, suggesting incomplete repair of radiation damage d ue to the larger fraction sizes. The survival for the sensitive cell line w as lower at small doses, but then it increased until it was equivalent to t hat after low-dose-rate irradiation for some fractionation schemes. The sen sitive cell line showed equivalence only with the 1.6-Gy fraction every 3 h , although 0.53 Gy every Ih and 1.1 Gy every 2 h showed equivalence at lowe r doses. This cell line also showed an adaptive response. The normal cell l ine showed a sensitization to the pulsed-dose-rate schemes compared to led- dose-rate irradiation. These data indicate that the response to pulsed-dose -rate irradiation is dependent on the cell line and that compared to the re sponse to low-dose-rate irradiation, it shows some equivalence with the res istant carcinoma cell line, an adaptive response with the parental carcinom a cell line, and sensitization with the normal cells. Therefore, further ev aluation is required before implementing pulsed-dose-rate irradiation in th e clinic. (C) 2000 by Radiation Research Society.