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头颈部癌症中 DNA 双链断裂修复效率的评估。

Evaluation of DNA double strand breaks repair efficiency in head and neck cancer.

机构信息

Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.

出版信息

DNA Cell Biol. 2012 Mar;31(3):298-305. doi: 10.1089/dna.2011.1325. Epub 2011 Aug 29.

Abstract

Head and neck cancers (head and neck squamous cell carcinomas [HNSCC]) are a heterogeneous group of neoplasms with varying presenting symptoms, treatment, and expected outcome. There is a need to find an effective way of its treatment at the molecular level. Thus, we should identify the mechanism of cancer cell response to damaging agents' activity, especially at DNA level. Our major goal was to evaluate the efficacy of DNA double strand breaks (DSBs) repair in HTB-43 and SCC-25 cancer cell lines as well as lymphocytes taken from HNSCC patients and healthy donors. The DNA repair efficiency was measured by neutral comet assay as well as extrachromosomal assay for DNA DSBs repair (TAK assay). We determined the levels of two main pathways of DNA DSBs-nonhomologous end joining (NHEJ) and homologous recombination repair (HRR). Neutral comet assay was used for evaluation of DNA DSBs repair after treatment with genotoxic agents. DNA DSBs induced by gamma radiation were repaired slower in lymphocytes from HNSCC patients than in lymphocytes from healthy controls. HTB-43 and SCC-25 cancer cell lines have higher efficacy of NHEJ and HRR than lymphocytes taken from patients as well as control subjects. Our results confirm the necessity of further studies on the mechanisms of DNA DSBs repair to provide insight into the molecular basis of head and neck cancer, which will allow us to improve methods of HNSCC treatment.

摘要

头颈部癌症(头颈部鳞状细胞癌[HNSCC])是一组异质性的肿瘤,其表现症状、治疗方法和预期结果各不相同。因此,我们需要在分子水平上找到一种有效的治疗方法。因此,我们应该确定癌细胞对损伤剂活性的反应机制,特别是在 DNA 水平上。我们的主要目标是评估 HTB-43 和 SCC-25 癌细胞系以及来自 HNSCC 患者和健康供体的淋巴细胞中 DNA 双链断裂(DSBs)修复的疗效。DNA 修复效率通过中性彗星试验以及用于 DNA DSBs 修复的染色体外试验(TAK 试验)来测量。我们确定了 DSBs 的两条主要修复途径——非同源末端连接(NHEJ)和同源重组修复(HRR)的水平。中性彗星试验用于评估基因毒性剂处理后 DNA DSBs 的修复。与健康对照组相比,来自 HNSCC 患者的淋巴细胞中由 γ 射线诱导的 DNA DSBs 的修复速度较慢。HTB-43 和 SCC-25 癌细胞系的 NHEJ 和 HRR 修复效率高于来自患者和对照的淋巴细胞。我们的结果证实了进一步研究 DNA DSBs 修复机制的必要性,以深入了解头颈部癌症的分子基础,这将使我们能够改进 HNSCC 的治疗方法。

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