title: Evaluation of the fullerene compound DF-1 as a radiation protector.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Building 10 CRC/B2-3500, Bethesda, MD 20892, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Brown
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Chung
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Urick
authors.forename: William P
authors.initials: WP
authors.lastname: Shield
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.forename: Angela
authors.initials: A
authors.lastname: Thetford
authors.forename: Uma T
authors.initials: UT
authors.lastname: Shankavaram
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Citrin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects; D037741:Fullerenes / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D037741:Fullerenes; D011837:Radiation-Protective Agents
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