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

Abstract

BackgroundFullerene 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.MethodsIn 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.ResultsDF-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.ConclusionsDF-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.

Accelerated hematopoietic recovery with angiotensin-(1–7) after total body radiation

“…Treatment with A(1–7) in this study starting 48 h after TBI and where no bleeding was done, improved survival at all doses of A(1–7) tested (Figure 10). The LD 50/30 for survival after TBI is in the range of 7.75–8.3 GY in this strain (Day et al 2008, Brown et al 2010). We found that 40% of TBI mice succumbed by 30 days if no A(1–7) was administered and this is consistent with the data of Brown and of Day mentioned above (or 60% of mice survived).…”

Perspectives of Fullerene Derivatives in PDT and Radiotherapy of Cancers

“…The process includes decrease of ROS level, inhibition of radiation-induced apoptosis and cells necrosis, DNA damages, oxidative stress. However, the process is not selective, because no difference between modest protective effect of the dendro-fullerene on normal fibroblasts (dose modifying factor=1.1 [99]) and on tumor cells was observed in vivo. LD 50/30 for mice, received 300 mg/kg of the dendro-fullerene before irradiation, was equal to 10.09 Gy in comparison with 8.29 Gy for control group.…”

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…The hallmark late effect of radiation exposure in several experimental animals is fibrosis, which is often permanent (Han et al, 2006;Lee et al, 2009;Flechsig et al, 2010;Qiu et al, 2011;Gorshkova et al, 2012;Cho et al, 2013;Ding et al, 2013;Horton et al, 2013). A number of chemical agents showed mitigation to radiation-induced injuries in animal models (Gandhi and Nair, 2004;Parihar et al, 2007;Thotala et al, 2009;Brown et al, 2010;Gao et al, 2012;Kma et al, 2012;Peebles et al, 2012;Alok et al, 2013;Copp et al, 2013).…”