Gridley D S, Glisson W C, Uhm J R
Department of Microbiology, Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, Loma Linda University School of Medicine, CA 92350, USA.
Ther Immunol. 1994 Jan;1(1):25-31.
Recent reports demonstrating that the lethal effects of radiation on tumour cells can be augmented by tumour necrosis factor-alpha (TNF-alpha) prompted us to investigate whether this premise holds true for the LS174T human colon adenocarcinoma cell line. Three different techniques were used to assess cell damage: 3H-thymidine (3H-TdR) uptake, clonogenic survival, and vital dye exclusion. In these assays human recombinant TNF-alpha treatment was administered before single-dose-gamma-radiation at 4, 6, 8, or 10 Gy. Oxygen radical formation by the tumour cells in the presence of TNF-alpha and radiation, alone and in combination, was also investigated. TNF-alpha and radiation, when used as single modalities, decreased LS174T cell viability with time. However, treatment with TNF-alpha before irradiation resulted in highly significant reductions in 3H-TdR uptake and decreased clonogenic survival compared to their counterparts receiving only radiation. Our data show that these two measurements of tumour-cell damage correlate well. No difference was noted in vital dye exclusion when comparisons were made between TNF-alpha+radiation and radiation alone. This latter finding may be partly due to the fact that although apoptotic cells are 'dead', they generally do not become more permeable to normally excluded macromolecules. Chemiluminescence measurements indicate that the radiation-enhancing mechanism of TNF-alpha may be related to oxygen radical production by the LS174T cells. Taken together our results suggest that TNF-alpha may be useful as an adjunctive modality in the radiotherapy of colon cancer.
最近的报告表明，肿瘤坏死因子-α（TNF-α）可增强辐射对肿瘤细胞的致死作用，这促使我们研究这一前提对于LS174T人结肠腺癌细胞系是否成立。我们使用了三种不同的技术来评估细胞损伤：3H-胸腺嘧啶核苷（3H-TdR）摄取、克隆形成存活率和活体染料排斥试验。在这些试验中，在4、6、8或10 Gy的单剂量γ辐射前给予人重组TNF-α治疗。我们还研究了在单独或联合使用TNF-α和辐射的情况下肿瘤细胞中氧自由基的形成。TNF-α和辐射单独使用时，会随时间降低LS174T细胞活力。然而，与仅接受辐射的对照组相比，照射前用TNF-α治疗导致3H-TdR摄取显著降低，克隆形成存活率下降。我们的数据表明，这两种肿瘤细胞损伤测量方法具有良好的相关性。在比较TNF-α+辐射组和单纯辐射组时，活体染料排斥试验未发现差异。后一发现可能部分是由于尽管凋亡细胞是“死亡的”，但它们通常不会对正常情况下被排斥的大分子变得更具通透性。化学发光测量表明，TNF-α的辐射增强机制可能与LS174T细胞产生氧自由基有关。综合我们的结果表明，TNF-α可能作为结肠癌放射治疗的辅助手段有用。
