Fullerenes as a new class of radioprotectors.
OBJECTIVE
To evaluate the radioprotective activity of C3, a regioisomer of water-soluble carboxyfullerene and a potent free radical scavenger, on both normal and tumour cells.


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 microg/ml) of C3 at 37 degrees C for 30 min before they were irradiated. Clonogenic assays were used to determine survival. The protection factor (PF), defined as the ratio of survival with and without C3, was then determined.


RESULTS
C3 protected GM-CFC in a concentration-dependent manner up to 50 microg/ml, and no additional protection was seen at 100 microg/ml. The PF was 1.77 when bone-marrow cells were pre-exposed to 50 microg/ml of C3 before they were irradiated with 2 Gy. The value of PF increased to 2.38 when 4 Gy was used. In sharp contrast, C3 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 microg/ml of C3. These values increased to 1.40, 1.75 and 1.27, respectively, when 4Gy was given. The dose-modifying factors at 10% survival were 1.37 and 1.15 for GM-CFC and EAT-PC, respectively.


CONCLUSIONS
C3 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 C3 and other water-soluble fullerenes have a potential to be a new class of cytoprotectors.
Department of Radiology, Washington University Medical School, St Louis, Missouri 63110, USA. lin@radonc.wustl.edu
H S
HS
Lin
T S
TS
Lin
R S
RS
Lai
T
T
D'Rosario
T Y
TY
Luh
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002244:Carbon / Q000737:chemistry* / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000532:radiotherapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006098:Granulocytes / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D009000:Monocytes / Q000528:radiation effects; D009368:Neoplasm Transplantation; D011837:Radiation-Protective Agents / Q000737:chemistry* / Q000627:therapeutic use*; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011837:Radiation-Protective Agents; D002244:Carbon