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  • 1. de Oliveira Galvão, Marcos Felipe
    et al.
    Sadiktsis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Batistuzzo de Medeiros, Silvia R.
    Dreij, Kristian
    DNA damage signaling and genotoxic effects induced by complex mixtures of PAHs generated by biomass burning air particulate matter in human lung cells2019Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 314, nr SI, s. S132-S133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most research concerning the effects of air pollutants on human health focuses on urban centers and on the role of vehicular and industrial emissions as major sources of pollution. However, approximately 3 billion people world-wide are exposed to air pollution from biomass burning [1]. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic and social activity worldwide [2,3], was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and their oxy-PAH derivatives; ii) time-dependent activation of DNA damage signaling and genotoxic effects, and iii) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8-10 ng/m3), while among oxy-PAHs, benzanthrone and 9,10-anthraquinone were the most abundant. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Peq). IC50 values for viability was 5.7 and 3.0 nM B[a]Peq at 24 h and 48 h, respectively. Based on this, all other experiments were conducted at doses up to 2 nM B[a]Peq. At these low doses, we observed a dose-dependent activation of DNA damage signaling (phosphorylation of Chk1) and genotoxicity (double strand breaks). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no other study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro [4], in lung cells exposed to biomass burning extracts. Persistent increased gene expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), inflammation (IL-8, TNF-α), cell cycle arrest (CDKN1A), and DNA repair (DDB2) was also identified. In conclusion, our data show high potency of biomass burning PM to induce cellular stress including genotoxicity, and more potently so when compared to B[a]P alone. Our study provides new data that will help elucidate the mechanism of lung cancer development associated with biomass burning. In addition, the results of this study support the establishment of new guidelines for human health protection in regions strongly impacted by biomass burning.

  • 2. de Oliveira Galvão, Marcos Felipe
    et al.
    Sadiktsis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Batistuzzo de Medeiros, Silvia Regina
    Dreij, Kristian
    Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting2020Ingår i: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 256, artikel-id 113381Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter(PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8–10 ng/m3), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Peq). IC50 values for viability were 5.7 and 3.0 nM B[a]Peq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 – Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2,COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.

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