@article{
author = "Isaković, Aleksandra J. and Marković, Zoran M. and Todorović-Marković, Biljana and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Mirković, Marija D. and Dramićanin, Miroslav and Harhaji, Ljubica M. and Raičević, Nevena and Nikolić, Zoran M. and Trajković, Vladimir S.",
year = "2006",
abstract = "The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C-60) and water-soluble polyhydroxylated fullerene [C-60(OH)(n)] were investigated. Crystal violet assay for cell viability demonstrated that nano-C-60 was at least three orders of magnitude more toxic than C-60(OH)(n) to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C-60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C-60(OH)(n) caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C-60 toxicity, but not C-60(OH)(n) toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C-60(OH)(n)-induced apoptosis, but not nano-C-60-mediated necrosis. Finally, C-60(OH)(n) antagonized, while nano-C-60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C-60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C-60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.",
journal = "Toxicological Sciences",
title = "Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene",
volume = "91",
number = "1",
pages = "173-183",
doi = "10.1093/toxsci/kfj127"
}