title: Investigation on cobalt-oxide nanoparticles cyto-genotoxicity and inflammatory response in two types of respiratory cells.
abstract: The increasing use of cobalt oxide (Co3 O4 ) nanoparticles (NPs) in several applications and the suggested genotoxic potential of Co-oxide highlight the importance of evaluating Co3 O4 NPs toxicity. Cyto-genotoxic and inflammatory effects induced by Co3 O4 NPs were investigated in human alveolar (A549), and bronchial (BEAS-2B) cells exposed to 1-40 µg ml(-1) . The physicochemical properties of tested NPs were analysed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA damage was assessed by the Formamido-pyrimidine glycosylase (Fpg)-modified comet assay and inflammation by interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) release (ELISA). In A549 cells, no cytotoxicity was found, whereas BEAS-2B cells showed a viability reduction at 40 µg ml(-1) and early membrane damage at 1, 5 and 40 µg ml-1. In A549 cells, direct and oxidative DNA damage at 20 and 40 µg ml(-1) were detected without any effects on cytokine release. In BEAS-2B cells, significant direct DNA damage at 40 µg ml(-1) and significant oxidative DNA damage with a peak at 5 µg ml(-1) , that was associated with increased TNF-α release at 1 µg ml(-1) after 2 h and increased IL-8 release at 20 µg ml(-1) after 24 h, were detected. The findings show in the transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20 and 40 µg ml(-1) . In normal bronchial cells, moderate cytotoxicity, direct DNA damage only at the highest concentration and significant oxidative-inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic-oxidative potential of Co3 O4 NPs and show greater sensitivity of BEAS-2B cells to cytotoxic and oxidative-inflammatory effects suggesting the use of different cell lines and multiple end-points to elucidate Co3 O4 NPs toxicity.
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Cavallo
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Aureliano
authors.initials: A
authors.lastname: Ciervo
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fresegna
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maiello
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tassone
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Buresti
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Casciardi
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Iavicoli
authors.affiliation: INAIL - Italian Workers' Compensation Authority - Research Area, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via Fontana Candida 1, 00040, Monteporzio Catone, Rome, Italy.
authors.forename: Cinzia Lucia
authors.initials: CL
authors.lastname: Ursini
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000473:pathology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology; D012137:Respiratory System / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D009153:Mutagens; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; D003035:Cobalt; C060728:cobalt oxide
keywords: comet assay; cytokine; cytotoxicity; direct-oxidative DNA damage; nanosized Co3O4