Dataset Information

Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549).

ABSTRACT: We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 ?M), 1-NP (1 and 10 ?M) and 3-NBA (0.5 and 5 ?M). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH) nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.

SUBMITTER: Rossner P

PROVIDER: S-EPMC5037673 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549).

Rossner Pavel P Strapacova Simona S Stolcpartova Jitka J Schmuczerova Jana J Milcova Alena A Neca Jiri J Vlkova Veronika V Brzicova Tana T Machala Miroslav M Topinka Jan J

International journal of molecular sciences 20160826 9

We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM), 1-NP (1 and 10 μM) and 3-NBA (0.5 and 5 μM). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bu ...[more]

PMID: 27571070

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Project description:BACKGROUND:While exposure to diesel exhaust particles has been linked to aberrant immune responses in allergic diseases such as asthma, little attention has been paid to their effects on the airway epithelial barrier. In this study, we sought to determine the effect of diesel exhaust exposure on airway epithelial barrier function and composition using in vitro and in vivo model systems. METHODS:16HBE14o- human bronchial epithelial cells were grown on collagen coated Transwell inserts and exposed to 5 to 50??g/cm2 SRM 2975 diesel particulate matter (DEP) suspended in cell culture medium or vehicle controls. Changes in barrier function were assessed by measuring transepithelial electrical resistance (TEER) and permeability to 4?kDa FITC Dextran. Neonatal BALB/c mice were exposed to aerosolized DEP (255?±?89??g/m3; 2?h per day for 5?days) and changes in the tight junction protein Tricellulin were assessed 2 weeks post exposure. RESULTS:A six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentration-dependent reduction in epithelial barrier integrity as measured by decreased TEER and increased permeability to 4?kDa FITC-Dextran. This reduction in epithelial barrier integrity corresponded to a significant reduction in expression of the tight junction protein Tricellulin. siRNA mediated knockdown of Tricellulin recapitulated changes in barrier function caused by DEP exposure. Neonatal exposure to aerosolized DEP caused a significant reduction in lung Tricellulin 2 weeks post exposure at both the protein and mRNA level. CONCLUSION:Short term exposure to DEP causes a significant reduction in epithelial barrier integrity through a reduction in the tight junction protein Tricellulin. Neonatal exposure to aerosolized DEP caused a significant and sustained reduction in Tricellulin protein and mRNA in the lung, suggesting that early life exposure to inhaled DEP may cause lasting changes in airway epithelial barrier function.

Dataset Information

Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549).

Publications

Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549).

Similar Datasets

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