期刊
NANOTOXICOLOGY
卷 8, 期 5, 页码 485-507出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2013.801089
关键词
lung; neoplastic transformation; invasion; genome expression; microarray
资金
- National Institute for Occupational Safety and Health
- National Occupational Research Agenda [NORA FY09 LMW6]
- National Institutes of Health [R01-HL095579]
- National Science Foundation [EPS-1003907]
- Office Of The Director
- Office of Integrative Activities [1003907] Funding Source: National Science Foundation
Accumulating evidence indicates that carbon nanotubes (CNTs) are biopersistent and can cause lung damage. With similar fibrous morphology and mode of exposure to asbestos, a known human carcinogen, growing concern has arisen for elevated risk of CNT-induced lung carcinogenesis; however, relatively little is known about the long-term carcinogenic effect of CNT. Neoplastic transformation is a key early event leading to carcinogenesis. We studied the ability of single-and multi-walled CNTs to induce neoplastic transformation of human lung epithelial cells compared to asbestos. Long-term (6-month) exposure of the cells to occupationally relevant concentrations of CNT in culture caused a neoplastic-like transformation phenotype as demonstrated by increased cell proliferation, anchorage-independent growth, invasion and angiogenesis. Whole-genome expression signature and protein expression analyses showed that single-and multi-walled CNTs shared similar signaling signatures which were distinct from asbestos. These results provide novel toxicogenomic information and suggest distinct particle-associated mechanisms of neoplasia promotion induced by CNTs and asbestos.
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