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在具有分数剂量累积的人乳头瘤病毒阴性和人乳头瘤病毒阳性头颈部癌症中,辐射诱导的 DNA 损伤反应的特征差异。

Characteristic differences in radiation-induced DNA damage response in human papillomavirus-negative and human papillomavirus-positive head and neck cancers with accumulation of fractional radiation dose.

机构信息

Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.

Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, South Australia, Australia.

出版信息

Head Neck. 2021 Oct;43(10):3086-3096. doi: 10.1002/hed.26802. Epub 2021 Jul 8.

Abstract

BACKGROUND

Superior treatment responses by patients with human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC), compared to patients with HNSCC from other causes, drive biomarker research to optimize treatment. Most HNSCC patients receive radiation therapy delivered as a fractionated course. Changing HPV status in HNSCC from a positive prognostic marker to a predictive one requires biomarkers that capture cellular radiation response to cumulative dose.

METHODS

Nuclear enlargement, γH2AX expression and micronuclei count, were studied in six HNSCC cell lines after 4 Gy fractionated X-irradiation.

RESULTS

All HNSCC cell lines displayed altered cellular responses, indicating increasing inability to repair radiation damage with subsequent radiation fractions. Increases in nuclear area were significantly greater among HPV positive cell lines (207% and 67% for the HPV positive and HPV negative groups, respectively).

CONCLUSIONS

A different character of DNA repair dysfunction in the HPV positive group suggests greater chromosomal translocation with accumulated radiation dose.

摘要

背景

与其他原因导致的头颈部鳞状细胞癌(HNSCC)患者相比,人乳头瘤病毒(HPV)阳性的 HNSCC 患者具有更好的治疗反应,这促使人们开展生物标志物研究以优化治疗。大多数 HNSCC 患者接受分次放射治疗。要将 HPV 状态从预后良好的标志物转变为预测性标志物,需要能够捕获细胞对累积剂量的放射反应的生物标志物。

方法

在 4Gy 分割 X 射线照射后,研究了六种 HNSCC 细胞系中的核增大、γH2AX 表达和微核计数。

结果

所有 HNSCC 细胞系均显示出改变的细胞反应,表明随着后续放射剂量的增加,细胞修复放射损伤的能力逐渐下降。HPV 阳性细胞系的核面积增加更为显著(HPV 阳性和 HPV 阴性组分别为 207%和 67%)。

结论

HPV 阳性组中 DNA 修复功能障碍的特征不同,提示随着累积辐射剂量的增加,染色体易位的可能性更大。

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