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 microg/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.