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Evaluation of DNA Double Strand Breaks Repair Efficiency in Head and Neck Cancer

机译:DNA双链断裂修复头颈癌的效率的评价。

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摘要

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.
机译:头颈癌(头颈鳞状细胞癌[HNSCC])是一组异质性肿瘤,其表现症状,治疗方法和预期结果各不相同。需要寻找在分子水平上治疗其的有效方法。因此,我们应该确定癌细胞对破坏剂活性的反应机制,尤其是在DNA水平上。我们的主要目标是评估DNA双链断裂(DSB)修复在HTB-43和SCC-25癌细胞系以及从HNSCC患者和健康供体获得的淋巴细胞中的功效。通过中性彗星测定以及DNA DSB修复的染色体外测定(TAK测定)来测量DNA修复效率。我们确定了DNA DSB的两个主要途径的水平-非同源末端连接(NHEJ)和同源重组修复(HRR)。用遗传毒性剂处理后,使用中性彗星试验评估DNA DSB的修复。 HNSCC患者的淋巴细胞中,γ射线诱导的DNA DSB修复的速度比健康人的淋巴细胞中的修复慢。 HTB-43和SCC-25癌细胞系的NHEJ和HRR功效要比从患者以及对照组的淋巴细胞获得的功效高。我们的结果证实有必要进一步研究DNA DSB修复的机制,以深入了解头颈部癌的分子基础,这将使我们能够改进HNSCC的治疗方法。

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