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

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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 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 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.

No MeSH data available.


Relative mRNA levels (fold changes relative to the control) induced after treatment of A549 cells with benzo[a]pyrene, 1-nitropyrene and 3-nitrobenzanthrone. (A) AKR1C2, 4 h; (B) AKR1C2, 24 h; (C) COX2, 4 h; (D) COX2, 24 h. Data represent mean values ± standard deviation from two triplicates from two independent experiments (analyzed as n = 6). Asterisks denote significant (* p < 0.05) gene expression changes relative to the control. The control expression level of the respective gene is represented by an emboldened horizontal line.
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ijms-17-01393-f007: Relative mRNA levels (fold changes relative to the control) induced after treatment of A549 cells with benzo[a]pyrene, 1-nitropyrene and 3-nitrobenzanthrone. (A) AKR1C2, 4 h; (B) AKR1C2, 24 h; (C) COX2, 4 h; (D) COX2, 24 h. Data represent mean values ± standard deviation from two triplicates from two independent experiments (analyzed as n = 6). Asterisks denote significant (* p < 0.05) gene expression changes relative to the control. The control expression level of the respective gene is represented by an emboldened horizontal line.

Mentions: Although none of the test compounds increased AKR1C2 expression after 4-h treatment (Figure 7A), induction was observed for all chemicals and doses after the longer treatment period. 1-NP was identified as the most potent inducer of AKR1C2 expression (Figure 7B). Four-hour treatment of A549 cells with B[a]P and 3-NBA resulted in a significant decrease in COX2 expression (Figure 7C). This decrease was also observed after 24-h treatment with 1 μM B[a]P. 1-NP, particularly at the higher test dose, was a strong inducer of COX2 after 24-h incubation (Figure 7D).


Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549)
Relative mRNA levels (fold changes relative to the control) induced after treatment of A549 cells with benzo[a]pyrene, 1-nitropyrene and 3-nitrobenzanthrone. (A) AKR1C2, 4 h; (B) AKR1C2, 24 h; (C) COX2, 4 h; (D) COX2, 24 h. Data represent mean values ± standard deviation from two triplicates from two independent experiments (analyzed as n = 6). Asterisks denote significant (* p < 0.05) gene expression changes relative to the control. The control expression level of the respective gene is represented by an emboldened horizontal line.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037673&req=5

ijms-17-01393-f007: Relative mRNA levels (fold changes relative to the control) induced after treatment of A549 cells with benzo[a]pyrene, 1-nitropyrene and 3-nitrobenzanthrone. (A) AKR1C2, 4 h; (B) AKR1C2, 24 h; (C) COX2, 4 h; (D) COX2, 24 h. Data represent mean values ± standard deviation from two triplicates from two independent experiments (analyzed as n = 6). Asterisks denote significant (* p < 0.05) gene expression changes relative to the control. The control expression level of the respective gene is represented by an emboldened horizontal line.
Mentions: Although none of the test compounds increased AKR1C2 expression after 4-h treatment (Figure 7A), induction was observed for all chemicals and doses after the longer treatment period. 1-NP was identified as the most potent inducer of AKR1C2 expression (Figure 7B). Four-hour treatment of A549 cells with B[a]P and 3-NBA resulted in a significant decrease in COX2 expression (Figure 7C). This decrease was also observed after 24-h treatment with 1 μM B[a]P. 1-NP, particularly at the higher test dose, was a strong inducer of COX2 after 24-h incubation (Figure 7D).

View Article: PubMed Central - PubMed

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 &mu;M), 1-NP (1 and 10 &mu;M) and 3-NBA (0.5 and 5 &mu;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.

No MeSH data available.