Correlation of sensitizer enhancement ratio with bromodeoxyuridine concentration and exposure time in human cervical carcinoma cells treated with low dose rate irradiation.

Abstract

The effect of a range of bromodeoxyuridine concentrations and exposure times on the sensitizer enhancement ratio of two human cervical carcinoma cell lines treated with low rate irradiation was evaluated. Both cell lines show a linear, though different, dose response to low dose rate irradiation at dose rates up to 0.62 Gy/hr. Cells were pre-incubated with 0, 1, 5, or 10 microM bromodeoxyuridine for 0, 24, or 48 hr prior to low dose rate irradiation. Based on the survival of cells exposed to 4 Gy, delivered at 0.62 Gy/hr, a slope was determined for an exponential survival curve for each bromodeoxyuridine concentration and exposure time. Sensitizer enhancement ratios were calculated as the ratio of the slopes of the treated and untreated cells from a particular exposure time. Ratios increased linearly initially with a plateauing at higher levels with respect to the product of bromodeoxyuridine concentration and time of exposure for both cell lines with similar degrees of enhancement. A linear relationship has been noted previously for acute irradiation of hamster cells over a similar range of sensitizer concentrations and exposure times. At the highest dose-time points (540 microM-hr) ratios of greater than 2 were attained, which were comparable to results obtained following acute radiation exposures of V-79 cells. These results demonstrate that significant sensitizer enhancement ratios with low dose irradiation can be obtained in human tumor cells after exposures of 2 to 3 doubling times using relatively low concentrations of sensitizer.