Polycyclic aromatic hydrocarbons and their quinones modulate the metabolic profile and induce DNA damage in human alveolar and bronchiolar cells

Gurbani, Deepak; Bharti, Santosh Kumar; Kumar, Ashutosh; Pandey, Alok Kumar; Ana, Godson; Verma, Ambrish Kumar; Khan, Altaf; Patel, Devendra Kumar; Mudiam, Mohana Krishna Reddy; Jain, Swatantra Kumar; Roy, Raja; Dhawan, Alok

doi:10.1016/j.ijheh.2013.04.001

Cited by 59 publications

(24 citation statements)

References 47 publications

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“…By incorporating in vivo metabolic profiling with multivariate pattern recognition and pathway analysis, the metabolomics data revealed that BAA and BAQ exposures were strongly associated with changes known to affect protein biosynthesis, mitochondrial dysfunction (oxidative stress), neural development, disturbance in vascular development and cardiac development function (cardiac toxicity). These findings generally concur with previous transcriptomics studies associated with the toxicological responses and effects of other PAHs and oxygenated PAHs (Goodale et al, 2013; Gurbani et al, 2013; Jayasundara et al, 2014). Our results demonstrated the utility of LC-MS-based metabolomics combined with the developmental zebrafish model to provide deeper mechanistic insights into the connections between chemical exposure and profound effects on organisms.…”

Section: Discussionsupporting

confidence: 91%

Metabolomic analysis to define and compare the effects of PAHs and oxygenated PAHs in developing zebrafish

Elie

Choi

Nkrumah‐Elie

et al. 2015

Environmental Research

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Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives are ubiquitously present in diesel exhaust, atmospheric particulate matter and soils sampled in urban areas. Therefore, inhalation or non-dietary ingestion of both PAHs and oxy-PAHs are major routes of exposure for people; especially young children living in these localities. While there has been extensive research on the parent PAHs, limited studies exist on the biological effects of oxy-PAHs which have been shown to be more soluble and more mobile in the environment. Additionally, investigations comparing the metabolic responses resulting from parent PAHs and oxy-PAHs exposures have not been reported. To address these current gaps, an untargeted metabolomics approach was conducted to examine the in vivo metabolomic profiles of developing zebrafish (Danio rerio) exposed to 4 µM of benz[a]anthracene (BAA) or benz[a]anthracene-7, 12-dione (BAQ). By integrating multivariate, univariate and pathway analyses, a total of 62 metabolites were significantly altered after 5 days of exposure. The marked perturbations revealed that both BAA and BAQ affect protein biosynthesis, mitochondrial function, neural development, vascular development and cardiac function. Our previous transcriptomic and genomic data were incorporated in this metabolomics study to provide a more comprehensive view of the relationship between PAH and oxy-PAH exposures on vertebrate development.

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Section: Discussionsupporting

confidence: 91%

Metabolomic analysis to define and compare the effects of PAHs and oxygenated PAHs in developing zebrafish

Elie

Choi

Nkrumah‐Elie

et al. 2015

Environmental Research

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“…4) Fig. 3 Comet assay photographs of the liver (i), hearth (ii), and kidney (iii) cells exposed to PM 10 OE (×800) itself but also synergizes with the already known ones (Behndig et al 2006;Topinka et al 2008;Xue and Warshawsky 2005), all of them leading to cell metabolic disorders, mutagenesis, and cancer (André et al 2011;Carreras et al 2013;Goulaouic et al 2008;Gurbani et al 2013;Muñoz and Albores 2011;Xue and Warshawsky 2005).…”

Section: Discussionmentioning

confidence: 99%

“…However, while inhibition reduces the number of comets, DNA damage remains high. This allows us to deduce the presence of another damaging mechanism, probably related to one or several of the classical pathways such as dihydrodiol epoxides, radical cation, and activation through PAH-o-quinone (Gurbani et al 2013;Muñoz and Albores 2011;Xue and Warshawsky 2005). Despite the fact that other non-specific and enzymatic superoxide sources, like mitochondrial, were not determined, the superoxide production by this two enzymes when exposed to PAHs not only represents an important pathogenesis way by Finally, to analyze the relationship between both experiments, we calculated a Pearson correlation coefficient between chemiluminescence data and comet assay results.…”

Section: Discussionmentioning

confidence: 99%

Organic compounds present in airborne particles stimulate superoxide production and DNA fragmentation: role of NOX and xanthine oxidase in animal tissues

Busso

Silva

Carreras

2016

Environ Sci Pollut Res

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Suspended particulate matter trigger the production of reactive oxygen species. However, most of the studies dealing with oxidative damage of airborne particles focus on the effects of individual compounds and not real mixtures. In order to study the enzymatic superoxide production resulting from the exposition to a complex mixture, we derived organic extracts from airborne particles collected daily in an urban area and exposed kidney, liver, and heart mammal tissues. After that, we measured DNA damage employing the comet assay. We observed that in every tissue, NADPH oxidase and xanthine oxidase were involved in O2 (-) production when they were exposed to the organic extracts, as the lucigenin's chemiluminescence decays when enzymes were inhibited. The same trend was observed with the percentage of cells with comets, since DNA damage was higher when they were exposed to same experimental conditions. Our data allow us to hypothesize that these enzymes play an important role in the oxidative stress produced by PAHs and that there is a mechanism involving them in the O2 (-)generation.

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“…Phe and Fla show anti-androgenic effects and 1-naphthol and 2-naphthol may act as thyroid hormone receptor antagonists (Sun et al, 2008). Otherwise, PAH causing DNA damage may also result in the activation of apoptotic pathways, interference of transcription, DNA replication, or protein synthesis (Gurbani et al, 2013;Kuang et al, 2013;Wei et al, 2010).…”

Section: Developmental Effects Of Childhood Pah Exposurementioning

confidence: 99%

Association of polycyclic aromatic hydrocarbons (PAHs) and lead co-exposure with child physical growth and development in an e-waste recycling town

Liu

Huang

et al. 2015

Chemosphere

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Polycyclic aromatic hydrocarbons and their quinones modulate the metabolic profile and induce DNA damage in human alveolar and bronchiolar cells

Cited by 59 publications

References 47 publications

Metabolomic analysis to define and compare the effects of PAHs and oxygenated PAHs in developing zebrafish

Metabolomic analysis to define and compare the effects of PAHs and oxygenated PAHs in developing zebrafish

Organic compounds present in airborne particles stimulate superoxide production and DNA fragmentation: role of NOX and xanthine oxidase in animal tissues

Association of polycyclic aromatic hydrocarbons (PAHs) and lead co-exposure with child physical growth and development in an e-waste recycling town

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