Tishler R B, Geard C R
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, NY, NY 10032.
Int J Radiat Oncol Biol Phys. 1992;22(3):495-8. doi: 10.1016/0360-3016(92)90861-b.
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.
评估了一系列溴脱氧尿苷浓度和暴露时间对低剂量率照射处理的两种人宫颈癌细胞系敏化增强率的影响。两种细胞系在剂量率高达0.62 Gy/hr时，对低剂量率照射均呈现线性但不同的剂量反应。在低剂量率照射前，细胞分别用0、1、5或10 microM溴脱氧尿苷预孵育0、24或48小时。基于以0.62 Gy/hr给予4 Gy照射后细胞的存活情况，确定了每种溴脱氧尿苷浓度和暴露时间下指数存活曲线的斜率。敏化增强率计算为特定暴露时间下处理细胞和未处理细胞斜率的比值。对于两种细胞系，比值最初呈线性增加，在较高水平时趋于平稳，增强程度相似，与溴脱氧尿苷浓度和暴露时间的乘积有关。先前在类似的敏化剂浓度和暴露时间范围内，对仓鼠细胞进行急性照射时也发现了线性关系。在最高剂量 - 时间点（540 microM - 小时），比值大于2，这与V - 79细胞急性辐射暴露后获得的结果相当。这些结果表明，使用相对低浓度的敏化剂，在2至3个倍增时间的暴露后，人肿瘤细胞在低剂量照射下可获得显著的敏化增强率。
