title: Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes.
abstract: A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.
authors: Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
authors: Dongquan
authors: D
authors: Chen
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505 USA.
authors: Todd A
authors: TA
authors: Stueckle
authors: Department of Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 USA.
authors: Sudjit
authors: S
authors: Luanpitpong
authors: Department of Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 USA.
authors: Yon
authors: Y
authors: Rojanasakul
authors: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201 USA.
authors: Yongju
authors: Y
authors: Lu
authors: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505 USA.
authors: Liying
authors: L
authors: Wang
keywords: Gene expression; Lung; Microarray; Pathways; Single-walled carbon nanotubes; p53