title: Multiple modes of responses to air pollution particulate materials in A549 alveolar type II cells.
abstract: Exposure to components of air pollution may cause adverse effects on lung cellular and organ functions through several mechanisms. Cell death, altered gene expression including production of cytokines, and modifications of normal cellular processes are possible outcomes that may be independent or coupled. To assess the effects of materials representative of a variety of particulate components of air pollution on lung epithelium, a human cell line of type II origin (A549 cells) was exposed to these materials in vitro. Materials tested included carbon black (CB), diesel soot from two sources (DS), residual oil fly ash (ROFA), Ottowa Ambient Air particulate (OAA), silicon dioxide (SiO2), and nickel subsulfide (Ni3S2). Endpoints included loss of adherence measured by crystal violet staining (CV), lactate dehydrogenase release (LDH), release of interleukin-8 (IL-8) measured by ELISA, and alkaline phosphatase activity in the cells (APc) and released into the supernatant (APS). Nuclear morphology was also examined. SiO2 and Ni3S2 both caused dose-dependent acute toxicity as assessed by LDH and CV, and caused alterations in nuclear morphology consistent with apoptosis. However, much more IL-8 was released into the tissue culture supernatant by SiO2 at the same levels of cytotoxicity than by Ni3S2. Neither of these acutely toxic materials increased APc or APS, but the less cytotoxic materials caused very significant release of AP in the order OAA > DS > ROFA >> SiO2 = Ni3S2. OAA and, to a lesser extent, DS caused increases in mitotic fraction and increased CV staining, consistent with stimulation of proliferation. These results suggest multiple modes of responses to toxic materials and imply that a toxicological screening process should address these and possibly other endpoints.
authors.affiliation: Lovelace Respiratory Research Institute, PO Box 5890, Albuquerque, NM 87185, USA. jseagrav@lrri.org
authors.forename: J C
authors.initials: JC
authors.lastname: Seagrave
authors.forename: K J
authors.initials: KJ
authors.lastname: Nikula
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology / Q000633:toxicity*; D000469:Alkaline Phosphatase / Q000378:metabolism; D002244:Carbon / Q000494:pharmacology / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016209:Interleukin-8; D002244:Carbon; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase