title: Ultrafine airborne particles cause increases in protooncogene expression and proliferation in alveolar epithelial cells.
abstract: Exposure to ambient particulate matter (PM) is linked to increases in respiratory morbidity and exacerbation of cardiopulmonary diseases. However, the important components of PM and their mechanisms of action in lung disease are unclear. We demonstrate the development of dose-related proliferation and apoptosis after exposure of an alveolar epithelial cell line (C10) to PM or to ultrafine carbon black (ufCB), a component of PM. Ribonuclease protection assays demonstrated that increases in mRNA levels of the early response protooncogenes c-jun, junB, fra-1, and fra-2 accompanied cell proliferation at low concentrations of PM whereas apoptotic concentrations of PM caused transient increases in expression of fos and jun family members and dose responsive increases in mRNA levels of receptor-interacting protein, Fas-associated death domain, and caspase-8. Significant increases in steady-state mRNA levels of protooncogenes and apoptosis-associated genes, TNFR-associated death domain, and Fas were also observed after exposure of epithelial cells to ufCB, but not fine carbon black or glass beads, respectively, suggesting that the ultrafine particulate component of PM is critical to its biological activity.
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Timblin
authors.forename: Arti
authors.initials: A
authors.lastname: Shukla
authors.forename: Ingrid
authors.initials: I
authors.lastname: Berlanger
authors.forename: Kelly A
authors.initials: KA
authors.lastname: BeruBe
authors.forename: Andrew
authors.initials: A
authors.lastname: Churg
authors.forename: Brooke T
authors.initials: BT
authors.lastname: Mossman
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D051379:Mice; D023282:Nuclease Protection Assays; D011519:Proto-Oncogenes / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000393:Air Pollutants; D004396:Coloring Agents; D012333:RNA, Messenger