کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525457 1401486 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleCompromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleCompromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity
چکیده انگلیسی


- Every patient responds to radiotherapy in individual manner.
- Some suffer severe side-effects because of their intrinsic radiosensitivity.
- γ-H2AX assay can detect such patients.
- “RS map” allows judging radiosensitivity, based on post-irradiation γ-H2AX kinetics.

A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised. Five of the radiosensitive patients harboured LoF mutations in DNA repair genes. An extensive range of quantitative parameters of the γ-H2AX response were studied with the objective to establish a predictor for radiosensitivity status. The most powerful predictor was the combination of the fraction of the unrepairable component of γ-H2AX foci and repair rate in PBL, both derived from non-linear regression analysis of foci repair kinetics. We introduce a visual representation of radiosensitivity status that allocates a position for each patient on a two-dimensional “radiosensitivity map”. This analytical approach provides the basis for larger prospective studies to further refine the algorithm, ultimately to triage capability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 383, Issue 2, 28 December 2016, Pages 212-219
نویسندگان
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