Abstract 276: Appalachian mountaintop mining particulate matter induces malignant transformation and tumorigenesis of human lung epithelial cells

Abstract

Abstract Lung cancer is the leading cause of cancer death, and after smoking, environmental and occupational exposure is the major cause. West Virginia (WV), the biggest coal mining state in Appalachia, ranks the third highest rate of lung cancer incidence in the United States. Our epidemiological studies suggest that living near WV mountaintop coal mining (MTM) activities is a contributing factor of the high lung cancer risk. The purpose of this study was to investigate the effect of MTM particle exposure on cell transformation and tumorigenesis of human lung epithelial cells. Air particulate matter (PM) collected within one mile of active MTM site in Edwight, WV (PMMTM), consisting of silica (Si, 48%) and molybdenum (Mo, 29%) as major constituents, was used for cell exposure studies. As control, PM collected from the neighboring areas that do not have coal mining in Green Bank, WV (PMCON) was used. Chronic exposure (3 months) of non-tumorigenic human lung epithelial BEAS-2B cells to sub-cytotoxic concentration (1 μg/mL) of PMMTM, but not PMCON, was found to induce malignant transformation of the cells, as indicated by loss of contact inhibition and anchorage-independent cell growth. The PMMTM-transformed cells also induced tumor formation in vivo using a xenograft mouse model. Exposure to Mo (1 μg/mL), but not Si, similarly induced malignant transformation and tumorigenesis of the lung epithelial cells, suggesting that Mo may be a key contributing factor of PMMTM pathologic effects. Citation Format: Sudjit Luanpitpong, Juhua Luo, Travis Kneuckles, Michael Hendryx, Yon Rojanasakul. Appalachian mountaintop mining particulate matter induces malignant transformation and tumorigenesis of human lung epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 276. doi:10.1158/1538-7445.AM2014-276