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卤代嘧啶对人恶性胶质瘤低剂量率照射的增敏作用

Halogenated pyrimidine sensitization of low dose rate irradiation in human malignant glioma.

作者信息

McLaughlin P W, Mancini W R, Stetson P L, Greenberg H S, Nguyen N, Seabury H, Heidorn D B, Lawrence T S

机构信息

Dept. of Radiation Oncology, University of Michigan Medical Center, Ann Arbor 48109.

出版信息

Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):637-42. doi: 10.1016/0360-3016(93)90281-y.

Abstract

PURPOSE

To determine the potential advantage of combining halogenated pyrimidine radiosensitization and continuous low dose rate irradiation in human malignant glioma.

METHODS AND MATERIALS

An established glioma line (U-251) was incubated with 5-bromo-2-doxyuridine (BrdUrd) at clinically achievable concentrations at three dose rates of interest--100 cGy/min (typical of external beam therapy), 43 cGy/hr (typical of temporary afterloaded implants), and 12 cGy/hr (typical of permanent implants).

RESULTS

After exposure to 1 microM BrdUrd, the greatest enhancement ratio was seen at the 12 cGy/hr dose rate, implying a BrdUrd induced inverse dose rate effect independent of a G2M block. Under these conditions, the mean inactivation dose after 1 microM BrdUrd exposure was equivalent for 100 cGy/min and 12 cGy/hr.

CONCLUSION

These results support the use of halopyrimidines as sensitizers of temporary afterloaded and permanent implants.

摘要

目的

确定在人类恶性胶质瘤中联合卤代嘧啶放射增敏和连续低剂量率照射的潜在优势。

方法与材料

将已建立的胶质瘤细胞系(U - 251)与5 - 溴 - 2 - 脱氧尿苷(BrdUrd)在临床上可达到的浓度下,于三种感兴趣的剂量率下孵育——100 cGy/分钟(外照射治疗的典型剂量率)、43 cGy/小时(临时后装植入的典型剂量率)和12 cGy/小时(永久植入的典型剂量率)。

结果

在暴露于1 microM BrdUrd后,在12 cGy/小时的剂量率下观察到最大的增强率,这意味着BrdUrd诱导了与G2M期阻滞无关的逆剂量率效应。在这些条件下,暴露于1 microM BrdUrd后的平均失活剂量对于100 cGy/分钟和12 cGy/小时是等效的。

结论

这些结果支持使用卤代嘧啶作为临时后装和永久植入的增敏剂。

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