Comparative cyto-genotoxicity assessment of functionalized and pristine multiwalled carbon nanotubes on human lung epithelial cells.
Chemical functionalization extends CNT applications conferring them new functions, but could modify their toxicity. We compared cytotoxicity and genotoxic/oxidative effects of -OH functionalized and pristine MWCNTs to evaluated the influence of the functionalization exposing A549 cells to 1-40μg/ml of both MWCNTs for 2, 4 and 24h. Cytotoxicity was evaluated by MTT and LDH tests and apoptosis induction, direct/oxidative DNA damage by Fpg-modified comet assay. After 24h we found viability reduction significant at 20 and 40μg/ml for both the MWCNTs with a detectable viability reduction already at lower concentrations for MWCNTs. A significant LDH release was found only for MWCNTs. Significant apoptosis induction was found from 10μg/ml of MWCNT-OH. A concentration-dependent increase of direct DNA damage, significant at 40μg/ml of MWCNTs and beginning from 5μg/ml of MWCNT-OH was detected at all exposure times. Oxidative DNA damage was not observed for both CNTs. The results indicate a different cytotoxic mechanism, by membrane damage for MWCNTs and apoptosis for MWCNT-OH, that could be explained by a different cellular uptake. Moreover, we found an earlier genotoxic effect for MWCNT-OH. The findings suggest that further studies on functionalized CNTs are necessary before using them in several applications particularly in biomedical field.
INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational Medicine, via Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. c.ursini@inail.it
Cinzia Lucia
CL
Ursini
Delia
D
Cavallo
Anna Maria
AM
Fresegna
Aureliano
A
Ciervo
Raffaele
R
Maiello
Giuliana
G
Buresti
Stefano
S
Casciardi
Francesca
F
Tombolini
Stefano
S
Bellucci
Sergio
S
Iavicoli
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D006900:Hydroxylation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D037742:Nanotubes, Carbon; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue