The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes.
Because of the ability to induce cell death in certain conditions, the fullerenes (C(60)) are potential anticancer and toxic agents. The colloidal suspension of crystalline C(60) (nano-C(60), nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60)>EtOH/nC(60)>aqu/nC(60). Mathematical modelling of singlet oxygen ((1)O(2)) generation indicates that the (1)O(2)-quenching power (THF/nC(60)<EtOH/nC(60)<aqu/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could have important implications for toxicology and biomedical application of colloidal fullerenes.
Markovic
Zoran
Z
Vinca Institute of Nuclear Sciences, Belgrade, Serbia.
Todorovic-Markovic
Biljana
B
Kleut
Duska
D
Nikolic
Nadezda
N
Vranjes-Djuric
Sanja
S
Misirkic
Maja
M
Vucicevic
Ljubica
L
Janjetovic
Kristina
K
Isakovic
Aleksandra
A
Harhaji
Ljubica
L
Babic-Stojic
Branka
B
Dramicanin
Miroslav
M
Trajkovic
Vladimir
V
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids; D037741:Fullerenes / Q000633:toxicity*; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012997:Solvents
D003102:Colloids; D037741:Fullerenes; D017382:Reactive Oxygen Species; D012997:Solvents