Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts.
既往接受过放射治疗的癌症患儿面临着可能出现衰弱性或致命性副作用的风险。本研究旨在评估髓母细胞瘤放疗对曾接受照射的幼年绵羊肺活检原代成纤维细胞DNA双链断裂修复能力的长期影响。研究纳入三只对照绵羊和五只接受照射绵羊的活检样本。治疗组绵羊曾接受总剂量28 Gy的脊髓放疗，该剂量相当于儿童髓母细胞瘤的治疗剂量。照射后4年分别从高剂量区（HD，>18 Gy）和低剂量区（LD，<2 Gy）获取肺组织活检样本。共提取15个细胞系（6个对照系、4个LD系和5个HD系）。对细胞进行照射后，通过免疫荧光分析DNA双链断裂修复情况，并行克隆形成、台盼蓝染色及微核试验。与对照组相比，HD和LD细胞系在照射后24小时均显示出显著增多的残留γH2AX病灶，且pATM活性显著降低。克隆形成试验、台盼蓝染色及微核试验结果均无统计学显著差异。本研究表明，既往放射暴露可损害绵羊肺成纤维细胞的DNA双链断裂修复机制。
肿瘤(癌症)患者之家