title: Cytotoxicity and DNA-damage in human lung epithelial cells exposed to respirable alpha-quartz.
abstract: Occupational exposure to respirable crystalline silica is associated with the development of silicosis, lung cancer and airways diseases. In order to assess cytotoxic effects and direct-oxidative DNA damage induced by short-term exposure to different doses of respirable alpha-quartz (NIST SRM1878a), we conducted a study using A549 cells. The cells were exposed to alpha-quartz at 25, 50, 100 microg/ml for 4 h and analysed by scanning electron microscope (SEM) and LDH release assay for cytotoxic effect evaluation. Cells were also exposed to 10, 25, 50, 100 microg/ml of alpha-quartz for 2 h and 4 h and analysed by Fpg comet test to evaluate direct and oxidative DNA damage. SEM observations of treated cells showed bleb development at lower doses and alterations of microvilli morphology at the highest dose. A slight LDH release was found only at 100 microg/ml. Fpg comet test showed a dose-related oxidative DNA damage in cells exposed for 2 h to quartz. Cells exposed for 4h at the same concentrations showed a dose-related direct DNA damage and the presence of oxidative DNA damage at lower doses. The bleb induction on cell surface evidenced by SEM at lower doses correlates with the presence of oxidative DNA damage at 4 h. The cell surface modifications observed by SEM at 100 microg/ml indicate that high doses of quartz induce more evident cytotoxic effects confirmed by LDH analysis and correlate with the genotoxicity showed by comet assay.
authors.affiliation: Department of Occupational Hygiene, ISPESL, National Institute for Occupational Safety and Prevention, Via Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. carla.fanizza@ispesl.it
authors.forename: Carla
authors.initials: C
authors.lastname: Fanizza
authors.forename: Cinzia Lucia
authors.initials: CL
authors.lastname: Ursini
authors.forename: Emilia
authors.initials: E
authors.lastname: Paba
authors.forename: Aureliano
authors.initials: A
authors.lastname: Ciervo
authors.forename: Arianna
authors.initials: A
authors.lastname: Di Francesco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maiello
authors.forename: Paolo
authors.initials: P
authors.lastname: De Simone
authors.forename: Delia
authors.initials: D
authors.lastname: Cavallo
mesh_terms: D000336:Aerosols; D002460:Cell Line; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000737:chemistry* / Q000187:drug effects* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D018384:Oxidative Stress; D010316:Particle Size; D011791:Quartz / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology
chemical_list: D000336:Aerosols; D011791:Quartz; D007770:L-Lactate Dehydrogenase