Fullerenes as a new class of radioprotectors

Abstract

Purpose : To evaluate the radioprotective activity of C 3, a regioisomer of water-soluble carboxyfullerene and a potent free radical scavenger, on both normal and tumour cells. Materials and methods : The murine committed bone-marrow stem cells for both granulocytes and monocytes (GM-CFC) were used to represent normal cells. For tumour cells, murine Ehrlich ascites tumour cells grown in regular tissue culture (EAT-T) and in the peritoneal cavity of CD1 mice (EAT-PC) and human HeLa cells were used. Cells were preexposed to varying concentrations (1-100 μ g/ml) of C 3 at 37°C for 30min before they were irradiated. Clonogenic assays were used to determine survival. The protection factor (PF), defined as the ratio of survival with and without C 3, was then determined. Results : C 3 protected GM-CFC in a concentration-dependent manner up to 50 μ g/ml, and no additional protection was seen at 100 μ g/ml. The PF was 1.77 when bone-marrow cells were pre-exposed to 50 μ g/ml of C 3 before they were irradiated with 2 Gy. The value of PF increased to 2.38 when 4 Gy was used. In sharp contrast, C 3 exerted less radioprotective effect on tumour cells. The PF values were 1.07, 1.43 and 1.07 for EAT-T, EAT-PC, and HeLa cells, respectively, when 2 Gy was given in the presence of 50 μ g/ml of C3. These values increased to 1.40, 1.75 and 1.27, respectively, when 4 Gy was given. The dose-modifying factors at 10% survival were 1.37 and 1.15 for GM-CFC and EAT-PC, respectively. Conclusion : C 3 exhibits a radioprotective effect on a class of normal haemopoietic progenitor cells. It also protects tumour cells, but to a lesser degree. It appears that C 3 and other watersoluble fullerenes have a potential to be a new class of cytoprotectors.