title: Appalachian mountaintop mining particulate matter induces neoplastic transformation of human bronchial epithelial cells and promotes tumor formation.
abstract: 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 (PMMTM) exposure on human bronchial epithelial cells. Our results show that chronic exposure (3 months) to noncytotoxic, physiological relevant concentration (1 μg/mL) of PMMTM, but not control particle PMCON, induced neoplastic transformation, accelerated cell proliferation, and enhanced cell migration of the exposed lung cells. Xenograft transplantation of the PMMTM-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 PMMTM. Chronic exposure to the main inorganic chemical constituent of PMMTM, molybdenum but not silica, similarly induced cell transformation and tumor promotion, suggesting the contribution of molybdenum, at least in part, in the PMMTM effects. These results provide new evidence for the carcinogenic potential of PMMTM and support further risk assessment and implementation of exposure control for PMMTM.
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University , Morgantown, West Virginia 26506, United States.
authors.forename: Sudjit
authors.initials: S
authors.lastname: Luanpitpong
authors.forename: Michael
authors.initials: M
authors.lastname: Chen
authors.forename: Travis
authors.initials: T
authors.lastname: Knuckles
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Juhua
authors.initials: J
authors.lastname: Luo
authors.forename: Emily
authors.initials: E
authors.lastname: Ellis
authors.forename: Michael
authors.initials: M
authors.lastname: Hendryx
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
mesh_terms: D000818:Animals; D001061:Appalachian Region; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000473:pathology; D003032:Coal Mining / Q000379:methods*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D016513:Mice, SCID; D008982:Molybdenum / Q000633:toxicity; D052638:Particulate Matter / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity; D036401:Toxicity Tests, Chronic / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D002273:Carcinogens; D052638:Particulate Matter; D012822:Silicon Dioxide; D008982:Molybdenum