Radiation Oncology Branch, National Cancer Institute, Building 10 CRC/B2-3500, Bethesda, MD 20892, USA.
Radiat Oncol. 2010 May 11;5:34. doi: 10.1186/1748-717X-5-34.
Fullerene compounds are known to possess antioxidant properties, a common property of chemical radioprotectors. DF-1 is a dendrofullerene nanoparticle with antioxidant properties previously found to be radioprotective in a zebrafish model. The purpose of this study was to evaluate the radioprotective effects of DF-1 in a murine model of lethal total body irradiation and to assess for selective radioprotection of normal cells versus tumor cells.
In vitro radioresponse was evaluated with clonogenic assays with human tumor cells and fibroblast lines in the presence of varying concentrations of DF-1 or vehicle. DNA double strand break induction and repair was evaluated with immunocytochemistry for gammaH2AX. Lethal total body irradiation was delivered with 137Cs after intraperitoneal delivery of DF-1 or vehicle control. Bone marrow hypoxia was evaluated with piminidazole uptake assessed by flow cytometry.
DF-1 provided modest radioprotection of human cancer cell lines and fibroblast cell lines when delivered prior to irradiation (dose modifying factor or 1.1). There was no evidence of selective protection of fibroblasts versus tumor cells. Cells treated with DF-1 at radioprotective doses were found to have fewer gammaH2AX foci at 1 and 6 hours after irradiation compared to vehicle treated controls. The LD50/30 for C57Bl6/Ncr mice treated with a single 300 mg/kg dose of DF-1 pre-irradiation was 10.09 Gy (95% CI 9.58-10.26) versus 8.29 Gy (95% CI, 8.21-8.32) for control mice. No protective effects were seen with a single 200 mg/kg dose. No increase in pimonidazole uptake was appreciated in bone marrow of mice treated with DF-1 compared to vehicle controls.
DF-1 has modest activity as a radiation protector in vivo. There was no evidence of selective protection from irradiation of normal versus tumor cells with DF-1.
富勒烯化合物具有抗氧化特性，这是化学辐射防护剂的共同特性。DF-1 是一种树状富勒烯纳米颗粒，具有抗氧化特性，先前在斑马鱼模型中被发现具有辐射防护作用。本研究旨在评估 DF-1 在致死全身照射的小鼠模型中的辐射防护作用，并评估其对正常细胞与肿瘤细胞的选择性辐射防护作用。
通过含有不同浓度 DF-1 或载体的克隆形成测定法评估体外放射反应，用免疫细胞化学法检测γH2AX 评估 DNA 双链断裂的诱导和修复。用 137Cs 进行致死全身照射，照射前经腹腔给予 DF-1 或载体对照。用流式细胞术评估 piminidazole 摄取评估骨髓缺氧。
DF-1 在照射前给予时，对人癌细胞系和成纤维细胞系提供适度的辐射防护作用（剂量修正因子或 1.1）。没有证据表明对成纤维细胞与肿瘤细胞的选择性保护。与用载体处理的对照相比，用放射防护剂量处理的细胞在照射后 1 和 6 小时时具有较少的γH2AX 焦点。经单次 300mg/kg 剂量的 DF-1 预处理照射的 C57Bl6/Ncr 小鼠的 LD50/30 为 10.09Gy（95%CI 9.58-10.26），而对照小鼠为 8.29Gy（95%CI，8.21-8.32）。单次 200mg/kg 剂量未见保护作用。与载体对照相比，用 DF-1 处理的小鼠骨髓中未观察到 pimonidazole 摄取增加。
DF-1 作为体内辐射防护剂具有适度的活性。没有证据表明 DF-1 对正常细胞与肿瘤细胞的照射具有选择性保护作用。
