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人FaDu鳞状细胞癌分次照射期间亚致死损伤的修复

Recovery from sublethal damage during fractionated irradiation of human FaDu SCC.

作者信息

Petersen Cordula, Zips Daniel, Krause Mechthild, Völkel Wolfram, Thames Howard D, Baumann Michael

机构信息

Clinic of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology, Fetscherstr. 74, 01307 Dresden, Germany.

出版信息

Radiother Oncol. 2005 Mar;74(3):331-6. doi: 10.1016/j.radonc.2004.10.009.

Abstract

BACKGROUND AND PURPOSE

The present study addresses whether recovery of sublethal damage in tumours may change during fractionated irradiation in FaDu human squamous cell carcinoma and whether such an effect might contribute to the pronounced time factor of fractionated irradiation previously found in this tumour.

PATIENTS AND METHODS

FaDu tumours were transplanted s.c. into the right hind leg of NMRI nu/nu mice. Single doses or 2, 4, and 8 equal fractions in 3.5 days were applied in previously unirradiated tumours and after priming with 18 fractions of 3 Gy in 18 or 36 days. All irradiations were given under clamp hypoxic conditions. Experimental endpoints were tumour control dose 50% (TCD50) and alpha/ beta values without and after priming.

RESULTS

Without priming TCD50 increased with increasing number of fractions from 38.8 Gy (95% CI 35;45) after single dose irradiation to 54.0 Gy (42;57) after 8 fractions. No increase in TCD50 when given in 1, 2, 4, or 8 fractions in 3.5 days was found after priming with 18 3-Gy fractions in 18 and 36 days. After priming with 18 fractions in 18 days TCD50 remained constant at 25 Gy and after priming with 18 fractions in 36 days at 42 Gy. The alpha/beta ratio without priming was 68 Gy (42;127). After fractionated irradiation with 18 3-Gy fractions in 18 and 36 days the alpha/beta ratio increased to 317 Gy (38; infinity) and to infinite, respectively.

CONCLUSIONS

Our results indicate that clonogenic cells in FaDu tumours lose entirely their capacity to recover from sublethal radiation damage during fractionated irradiation. Therefore, an increased repair capacity as an explanation for the pronounced time factor of fractionated irradiation in this tumour can be ruled out.

摘要

背景与目的

本研究探讨在FaDu人鳞状细胞癌的分次照射过程中,肿瘤亚致死损伤的修复是否会发生变化,以及这种效应是否可能导致先前在该肿瘤中发现的明显的分次照射时间因素。

患者与方法

将FaDu肿瘤皮下移植到NMRI nu/nu小鼠的右后腿。在先前未照射的肿瘤中以及在18天或36天内给予18次3 Gy的预照射后,给予单次剂量或在3.5天内给予2、4和8个相等分次的照射。所有照射均在钳夹缺氧条件下进行。实验终点为肿瘤控制剂量50%(TCD50)以及预照射前后的α/β值。

结果

未预照射时,TCD50随着分次次数的增加而增加,从单次剂量照射后的38.8 Gy(95%可信区间35;45)增加到8次分次照射后的54.0 Gy(42;57)。在18天和36天内给予18次3 Gy的预照射后,在3.5天内给予1、2、4或8次分次照射时,未发现TCD50增加。在18天内给予18次分次预照射后,TCD50保持在25 Gy不变,在36天内给予18次分次预照射后,TCD50保持在42 Gy不变。未预照射时的α/β比值为68 Gy(42;127)。在18天和36天内给予18次3 Gy的分次照射后,α/β比值分别增加到317 Gy(38;无穷大)和无穷大。

结论

我们的结果表明,FaDu肿瘤中的克隆细胞在分次照射过程中完全丧失了从亚致死性辐射损伤中恢复的能力。因此,可以排除增加的修复能力作为该肿瘤中明显的分次照射时间因素的解释。

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