title: Cellular reactions to long-term volatile organic compound (VOC) exposures.
abstract: Investigations of cellular processes initiated by volatile organic compounds (VOCs) are limited when modelling realistic long-term exposure scenarios at low concentrations. Exposure to indoor VOCs is associated with a range of adverse effects, but data on molecular changes at regulatory threshold limits are lacking. Activity analysis of VOC in vitro can be a valuable complement to inhalation toxicological evaluations. We developed an exposure platform that generates a stable VOC atmosphere and allows the exposure of cells for longer periods. Using formaldehyde as a model analyte, air-liquid interface cultured A549 lung epithelial cells were exposed to critical concentrations of 0.1 and 0.5 ppm for 3 days. Owing to the lack of known exposure biomarkers, we applied a genome-wide transcriptional analysis to investigate cellular responses at these sublethal concentrations. We demonstrate a minor overlap of differentially expressed transcripts for both treatment concentrations, which can be further analyzed for their use as exposure biomarkers. Moreover, distinct expression patterns emerge for 0.1 and 0.5 ppm formaldehyde exposure, which is reflected in significant enrichment of distinct biological processes. More specifically, metabolism of specific compound classes, lipid biosynthesis and lung-associated functions are affected by lower exposure levels and processes affecting proliferation and apoptosis dominate the higher exposure levels.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.|Bioenergy 2020+, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zeisler
authors.affiliation: Division of Biomedical Sciences, Warwick Medical School, University of Warwick, UK.
authors.forename: Mohammad Tauqeer
authors.initials: MT
authors.lastname: Alam
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Gruber
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Becker
authors.affiliation: ATLAS Biolabs GmbH, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Neubert
authors.affiliation: Bioenergy 2020+, Graz, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Kleinhappl
authors.affiliation: Bioenergy 2020+, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Martini
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Überall
mesh_terms: D000072283:A549 Cells / Q000187:drug effects; D000393:Air Pollutants / Q000032:analysis*; D016902:Air Pollution, Indoor; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D004781:Environmental Exposure; D005557:Formaldehyde / Q000009:adverse effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D052638:Particulate Matter / Q000032:analysis; D012130:Respiratory Hypersensitivity; D014158:Transcription, Genetic; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D008055:Lipids; D052638:Particulate Matter; D055549:Volatile Organic Compounds; D005557:Formaldehyde