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Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappa B, and Akt in normal and malignant human mesothelial cells.

Authors
Pacurari-M; Yin-XJ; Zhao-JS; Ding-M; Leonard-SS; Schwegler-Berry-D; Ducatman-BS; Sbarra-D; Hoover-MD; Castranova-V; Vallyathan-V
Source
Environ Health Perspect 2008 Sep; 116(9):1211-1217
NIOSHTIC No.
20034590
Abstract
BACKGROUND: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells. OBJECTIVE: Exposure to asbestos is the primary cause of malignant mesothelioma in 80-90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. METHODS: In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor kappa B (NF-kappa B), and protein serine-threonine kinase (Akt). RESULTS: Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-kappa B, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure. CONCLUSIONS: The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.
Keywords
Pulmonary-system; Lung-function; Respirable-dust; Particulate-dust; Particulates; Toxic-effects; Toxicology; Biological-effects; Biological-systems; Cell-biology; Cell-metabolism; Cellular-function; Nanotechnology
Contact
Val Vallyathan, CDC, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505
CODEN
EVHPAZ
CAS No.
7440-44-0
Publication Date
20080901
Document Type
Journal Article
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
9
ISSN
0091-6765
NIOSH Division
HELD; DRDS
Priority Area
Manufacturing; Healthcare and Social Assistance
Source Name
Environmental Health Perspectives
State
WV
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