Appalachian Mountaintop Mining Particulate Matter Induces Neoplastic Transformation of Human Bronchial Epithelial Cells and Promotes Tumor Formation

[Image: see text] Epidemiological studies suggest that living near mountaintop coal mining (MTM) activities is one of the contributing factors for high lung cancer incidence. The purpose of this study was to investigate the long-term carcinogenic potential of MTM particulate matter (PM(MTM)) exposure on human bronchial epithelial cells. Our results show that chronic exposure (3 months) to noncytotoxic, physiological relevant concentration (1 μg/mL) of PM(MTM), but not control particle PM(CON), induced neoplastic transformation, accelerated cell proliferation, and enhanced cell migration of the exposed lung cells. Xenograft transplantation of the PM(MTM)-exposed cells in mice caused no apparent tumor formation, but promoted tumor growth of human lung carcinoma H460 cells, suggesting the tumor-promoting effect of PM(MTM). Chronic exposure to the main inorganic chemical constituent of PM(MTM), molybdenum but not silica, similarly induced cell transformation and tumor promotion, suggesting the contribution of molybdenum, at least in part, in the PM(MTM) effects. These results provide new evidence for the carcinogenic potential of PM(MTM) and support further risk assessment and implementation of exposure control for PM(MTM).