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

Simona Strapacova,Veronika Vlkova,Alena Milcova,Pavel Rossner,Jan Topinka,Tana Brzicova,Jitka Stolcpartova,Jiri Neca,Miroslav Machala,Jana Schmuczerova

doi:10.3390/ijms17091393

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.

Highlights

Environmental air pollution affects most of the human population
Despite substantial technological advances resulting in decreased fuel consumption and lower emissions, road traffic remains a significant source of air pollution, in metropolitan areas
From a complex mixture of chemicals and particles produced by incomplete combustion of organic material, including oil and oil products, polycyclic aromatic hydrocarbons (PAHs) are noteworthy due to their metabolism to reactive compounds that can bind to nucleic acids and proteins, cause their damage and/or loss of function, and induce mutations

Summary

Introduction

Air pollutants originate from three major sources: domestic heating, industrial activities, and traffic. Despite substantial technological advances resulting in decreased fuel consumption and lower emissions, road traffic remains a significant source of air pollution, in metropolitan areas. Apart from binding to macromolecules resulting in formation of PAH–DNA adducts or protein adducts, some PAHs may generate reactive oxygen species (ROS) and induce oxidative stress. Nitro-PAHs are characterized by persistence in the environment and high mutagenic and carcinogenic activities in model systems. Their concentrations in the environment are lower than those of parent PAHs, but some nitro-PAHs have been shown to act as direct mutagens that do not require metabolic activation [3]

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