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急性γ辐照后人癌症和角质形成细胞预处理和后处理效应的平行比较。

Parallel comparison of pre-conditioning and post-conditioning effects in human cancers and keratinocytes upon acute gamma irradiation.

机构信息

a Radiation Sciences , McMaster University , Hamilton , Canada.

b Department of Biology , McMaster University , Hamilton , Canada.

出版信息

Int J Radiat Biol. 2019 Feb;95(2):170-178. doi: 10.1080/09553002.2019.1547850. Epub 2019 Jan 4.

DOI:10.1080/09553002.2019.1547850
PMID:30496014
Abstract

PURPOSE

To determine and compare the effects of pre-conditioning and post-conditioning towards gamma radiation responses in human cancer cells and keratinocytes.

MATERIAL AND METHODS

The clonogenic survival of glioblastoma cells (T98G), keratinocytes (HaCaT), and colorectal carcinoma cells (HCT116 p53 and p53) was assessed following gamma ray exposure from a Cs-137 source. The priming dose preceded the challenge dose in pre-conditioning whereas the priming dose followed the challenge dose in post-conditioning. The priming dose was either 5 mGy or 0.1 Gy. The challenge dose was 0.5-5 Gy.

RESULTS

In both pre- and post-conditioning where the priming dose was 0.1 Gy and the challenge dose was 4 Gy, RAR developed in T98G but not in HaCaT cells. In HCT116 p53, pre-conditioning had either no effect or a radiosensitizing effect and whereas post-conditioning induced either radiosensitizing or radioadaptive effect. The different observed outcomes were dependent on dose, the time interval between the priming and challenge dose, and the time before the first irradiation. Post-conditioning effects could occur with a priming dose as low as 5 mGy in HCT116 p53 cells. When HCT116 cells had no p53 protein expression, the radiosensitizing or radioadaptive response by the conditioning effect was abolished.

CONCLUSIONS

The results suggest that radiation conditioning responses are complex and depend on at least the following factors: the magnitude of priming/challenge dose, the time interval between priming and challenge dose, p53 status, cell seeding time prior to the first radiation treatment. This work is the first parallel comparison demonstrating the potential outcomes of pre- and post-conditioning in different human cell types using environmentally and medically relevant radiation doses.

摘要

目的

确定并比较预处理和后处理对人类癌细胞和角质形成细胞伽马辐射反应的影响。

材料和方法

用 Cs-137 源照射后,评估神经胶质瘤细胞(T98G)、角质形成细胞(HaCaT)和结肠直肠癌细胞(HCT116 p53 和 p53)的集落存活情况。在预处理中,引发剂量先于挑战剂量,而在后处理中,引发剂量后于挑战剂量。引发剂量分别为 5 mGy 或 0.1 Gy。挑战剂量为 0.5-5 Gy。

结果

在预处理和后处理中,引发剂量为 0.1 Gy,挑战剂量为 4 Gy 的情况下,RAR 在 T98G 中发展,但在 HaCaT 细胞中没有。在 HCT116 p53 中,预处理要么没有效果,要么具有放射增敏作用,而在后处理中,要么诱导放射增敏作用,要么诱导放射适应性作用。不同的观察结果取决于剂量、引发剂量和挑战剂量之间的时间间隔以及第一次照射前的时间。在后处理中,HCT116 p53 细胞中只需 5 mGy 的引发剂量即可产生效应。当 HCT116 细胞没有 p53 蛋白表达时,条件作用的放射增敏或放射适应性反应被消除。

结论

结果表明,辐射处理反应是复杂的,至少取决于以下因素:引发/挑战剂量的大小、引发和挑战剂量之间的时间间隔、p53 状态、第一次放射治疗前的细胞播种时间。这项工作首次平行比较了使用环境和医学相关辐射剂量的不同人类细胞类型的预处理和后处理的潜在结果。

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