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Neoplastic Transformation of Human Bronchial Cells by Lead Chromate Particles

¹ Wise Laboratory of Environmental and Genetic Toxicology; ² Maine Center for Toxicology and Environmental Health, and Department of Applied Medical Sciences; and ³ Department of Mathematics and Statistics, University of Southern Maine, Portland, Maine

Correspondence and requests for reprints should be addressed to John P. Wise, Sr., Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, and Department of Applied Medical Sciences, University of Southern Maine, Portland, ME 04104. E-mail: john.wise{at}usm.maine.edu

Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen with widespread exposure among people in occupational settings and the general public. However, no studies have examined the chromate-induced malignant transformation of human lung epithelial cells, its predominant 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 µg/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 that chromosome instability may play an important role in particulate Cr(VI)-induced neoplastic transformation.

Key Words: lead chromate • neoplastic transformation • bronchial epithelial cells

CLINICAL RELEVANCE This is the first article to show neoplastic transformation by hexavalent chromium in human lung cells. It provides important information for better understanding of the mechanisms involved in human bronchial carcinogenesis induced by particulate chromate.