Hartel Carola, Nasonova Elena, Fuss Martina C, Nikoghosyan Anna V, Debus Juergen, Ritter Sylvia
GSI Helmholtzzentrum fuer Schwerionenforschung, Biophysics Department, Darmstadt, Germany.
Joint Institute for Nuclear Research (JINR), Laboratory of Radiation Biology, Dubna, Russia.
Clin Transl Radiat Oncol. 2018 Oct 10;13:57-63. doi: 10.1016/j.ctro.2018.10.002. eCollection 2018 Nov.
Chromosomal aberrations in peripheral blood lymphocytes are a biomarker for radiation exposure and are associated with an increased risk for malignancies. To determine the long-term cytogenetic effect of radiotherapy, we analyzed the persistence of different aberration types up to 2.5 years after the treatment.
Cytogenetic damage was analyzed in lymphocytes from 14 patients that had undergone C-ion boost + IMRT treatment for prostate cancer. Samples were taken immediately, 1 year and 2.5 years after therapy. Aberrations were scored using the multiplex fluorescence in situ hybridization technique and grouped according to their transmissibility to daughter cells.
Dicentric chromosomes (non-transmissible) and translocations (transmissible) were induced with equal frequencies. In the follow-up period, the translocation yield remained unchanged while the yield of dicentrics decreased to ≈40% of the initial value (p = 0.011 and p = 0.001 for 1 and 2.5 years after compared to end of therapy). In 2 patients clonal aberrations were observed; however they were also found in samples taken before therapy and thus were not radiotherapy induced.
The shift in the aberrations spectrum towards a higher fraction of translocations indicates the exposure of hematopoietic stem and progenitor cells underlining the importance of a careful sparing of bone marrow during radiotherapy to minimize the risk for secondary cancers.
外周血淋巴细胞中的染色体畸变是辐射暴露的生物标志物,且与恶性肿瘤风险增加相关。为了确定放射治疗的长期细胞遗传学效应,我们分析了治疗后长达2.5年不同畸变类型的持续存在情况。
对14例接受碳离子增强+调强适形放疗治疗前列腺癌的患者的淋巴细胞进行细胞遗传学损伤分析。在治疗后即刻、1年和2.5年采集样本。使用多重荧光原位杂交技术对畸变进行评分,并根据它们向子代细胞的传递性进行分组。
双着丝粒染色体(不可传递)和易位(可传递)以相同频率被诱导产生。在随访期间,易位发生率保持不变,而双着丝粒的发生率降至初始值的约40%(与治疗结束相比,治疗后1年和2.5年时p分别为0.011和0.001)。在2例患者中观察到克隆性畸变;然而,在治疗前采集的样本中也发现了这些畸变,因此并非由放射治疗诱导产生。
畸变谱向更高比例的易位转变表明造血干细胞和祖细胞受到了照射,这突出了在放射治疗期间小心保护骨髓以将继发癌症风险降至最低的重要性。