Published ahead of print on June 21, 2007, doi:10.1165/rcmb.2007-0058OC Am. J. Respir. Cell Mol. Biol., Volume 37, Number 5, November 2007, 544-552 A more recent version of this article appeared on November 1, 2007
Submitted on February 23, 2007 Neoplastic Transformation of Human Bronchial Cells by Lead Chromate ParticlesHong Xie1,1 Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, USA; Maine Center for Toxicology and Environmental Health, and Department of Applied Medical Sciences, University of Southern Maine, Portland, ME, USA, 2 Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, USA; Department of Mathematics and Statistics, University of Southern Maine, Portland, ME, USA, 3 Maine Center for Toxicology and Environmental Health, and Department of Applied Medical Sciences, University of Southern Maine, Portland, ME, USA; Department of Mathematics and Statistics, University of Southern Maine, Portland, ME, USA * To whom correspondence should be addressed. E-mail: john.wise{at}usm.maine.edu.
Particulate hexavalent chromium (Cr(VI)) is a well established human lung carcinogen with widespread exposure to people in occupational settings and to the general public. However, no studies have examined the chromate-induced malignant transformation of human lung epithelial cells, its predominate target. Human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells were used to better understand the mechanisms involved in human bronchial carcinogenesis induced by particulate chromate. We found that aneuploid cells increased in a concentration-dependent manner after chronic exposure to lead chromate. Moreover, chronic exposure to lead chromate induced BEP2D cell transformation. Transformed BEP2D cells developed through a series of sequential steps, including altered cell morphology, loss of cell contact inhibition and anchorage-independent growth. Specifically, a 5 day exposure to lead chromate induced foci formation with 0, 1, 5 and 10 ug/cm2 lead chromate inducing 0, 7, 3, and 15 foci in 10 dishes. Anchorage independence was observed in cell lines derived from these foci. These foci-derived cells also showed centrosome amplification and increases in aneuploid metaphases. Our study demonstrates that particulate Cr(VI) is able to transform human bronchial epithelial cells and chromosome instability may play a important role in particulate Cr(VI)-induced neoplastic transformation.
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