Most cited article - PubMed ID 24694657
Nonhomologous DNA end joining and chromosome aberrations in human embryonic lung fibroblasts treated with environmental pollutants
Gasoline engine emissions have been classified as possibly carcinogenic to humans and represent a significant health risk. In this study, we used MucilAir™, a three-dimensional (3D) model of the human airway, and BEAS-2B, cells originating from the human bronchial epithelium, grown at the air-liquid interface to assess the toxicity of ordinary gasoline exhaust produced by a direct injection spark ignition engine. The transepithelial electrical resistance (TEER), production of mucin, and lactate dehydrogenase (LDH) and adenylate kinase (AK) activities were analyzed after one day and five days of exposure. The induction of double-stranded DNA breaks was measured by the detection of histone H2AX phosphorylation. Next-generation sequencing was used to analyze the modulation of expression of the relevant 370 genes. The exposure to gasoline emissions affected the integrity, as well as LDH and AK leakage in the 3D model, particularly after longer exposure periods. Mucin production was mostly decreased with the exception of longer BEAS-2B treatment, for which a significant increase was detected. DNA damage was detected after five days of exposure in the 3D model, but not in BEAS-2B cells. The expression of CYP1A1 and GSTA3 was modulated in MucilAir™ tissues after 5 days of treatment. In BEAS-2B cells, the expression of 39 mRNAs was affected after short exposure, most of them were upregulated. The five days of exposure modulated the expression of 11 genes in this cell line. In conclusion, the ordinary gasoline emissions induced a toxic response in MucilAir™. In BEAS-2B cells, the biological response was less pronounced, mostly limited to gene expression changes.
- Keywords
- MucilAir™, air-liquid interface, bronchial epithelial cells, gasoline emissions, toxicity,
- MeSH
- Adenylate Kinase metabolism MeSH
- Bronchi cytology MeSH
- DNA Breaks, Double-Stranded MeSH
- Electric Impedance MeSH
- Epithelial Cells drug effects metabolism MeSH
- Cells, Cultured MeSH
- L-Lactate Dehydrogenase metabolism MeSH
- Humans MeSH
- Mucins metabolism MeSH
- Toxicity Tests methods MeSH
- Transcriptome MeSH
- Vehicle Emissions toxicity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenylate Kinase MeSH
- L-Lactate Dehydrogenase MeSH
- Mucins MeSH
- Vehicle Emissions MeSH
