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Open Access 01-12-2010 | Research

Evaluation of the fullerene compound DF-1 as a radiation protector

Authors: Aaron P Brown, Eun Joo Chung, Mary Ellen Urick, William P Shield III, Anastasia L Sowers, Angela Thetford, Uma T Shankavaram, James B Mitchell, Deborah E Citrin

Published in: Radiation Oncology | Issue 1/2010

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 γH2AX. 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 γH2AX 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.

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Title: Evaluation of the fullerene compound DF-1 as a radiation protector
Authors: Aaron P Brown
Eun Joo Chung
Mary Ellen Urick
William P Shield III
Anastasia L Sowers
Angela Thetford
Uma T Shankavaram
James B Mitchell
Deborah E Citrin
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2010
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-5-34

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluation of the fullerene compound DF-1 as a radiation protector

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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