2023
Holme, Jørn A.; Vondráček, Jan; Machala, Miroslav; Lagadic-Gossmann, Dominique; Vogel, Christoph F. A.; Ferrec, Eric Le; Sparfel, Lydie; Øvrevik, Johan
In: Biochemical pharmacology, vol. 216, pp. 115801, 2023, ISSN: 1873-2968 0006-2952, (Place: England).
Abstract | Links | BibTeX | Tags: *Air Pollutants/toxicity, *Lung Neoplasms/chemically induced/genetics, *Polycyclic Aromatic Hydrocarbons/toxicity, Air pollution, Aryl Hydrocarbon/genetics, Carcinogenesis, Diesel exhaust, Environmental Monitoring, Genotoxicity, Humans, Inflammation, Occupational exposure, Particulate Matter/toxicity, Receptors, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion
@article{holme_lung_2023,
title = {Lung cancer associated with combustion particles and fine particulate matter (PM(2.5)) - The roles of polycyclic aromatic hydrocarbons (PAHs) and the aryl hydrocarbon receptor (AhR).},
author = {Jørn A. Holme and Jan Vondráček and Miroslav Machala and Dominique Lagadic-Gossmann and Christoph F. A. Vogel and Eric Le Ferrec and Lydie Sparfel and Johan Øvrevik},
doi = {10.1016/j.bcp.2023.115801},
issn = {1873-2968 0006-2952},
year = {2023},
date = {2023-10-01},
journal = {Biochemical pharmacology},
volume = {216},
pages = {115801},
abstract = {Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% of all lung cancer deaths. Increased risk associated with living near trafficked roads, occupational exposure to diesel exhaust, indoor coal combustion and cigarette smoking, suggest that combustion components in ambient fine particulate matter (PM(2.5)), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers of lung cancer. Activation of the aryl hydrocarbon receptor (AhR) induces expression of xenobiotic-metabolizing enzymes (XMEs) and increase PAH metabolism, formation of reactive metabolites, oxidative stress, DNA damage and mutagenesis. Lung cancer tissues from smokers and workers exposed to high combustion PM levels contain mutagenic signatures derived from PAHs. However, recent findings suggest that ambient air PM(2.5) exposure primarily induces lung cancer development through tumor promotion of cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss the role of AhR and PAHs in lung cancer development caused by air pollution focusing on the tumor promoting properties including metabolism, immune system, cell proliferation and survival, tumor microenvironment, cell-to-cell communication, tumor growth and metastasis. We suggest that the dichotomy in lung cancer patterns observed between smoking and outdoor air PM(2.5) represent the two ends of a dose-response continuum of combustion PM exposure, where tumor promotion in the peripheral lung appears to be the driving factor at the relatively low-dose exposures from ambient air PM(2.5), whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.},
note = {Place: England},
keywords = {*Air Pollutants/toxicity, *Lung Neoplasms/chemically induced/genetics, *Polycyclic Aromatic Hydrocarbons/toxicity, Air pollution, Aryl Hydrocarbon/genetics, Carcinogenesis, Diesel exhaust, Environmental Monitoring, Genotoxicity, Humans, Inflammation, Occupational exposure, Particulate Matter/toxicity, Receptors, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion},
pubstate = {published},
tppubtype = {article}
}
Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% of all lung cancer deaths. Increased risk associated with living near trafficked roads, occupational exposure to diesel exhaust, indoor coal combustion and cigarette smoking, suggest that combustion components in ambient fine particulate matter (PM(2.5)), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers of lung cancer. Activation of the aryl hydrocarbon receptor (AhR) induces expression of xenobiotic-metabolizing enzymes (XMEs) and increase PAH metabolism, formation of reactive metabolites, oxidative stress, DNA damage and mutagenesis. Lung cancer tissues from smokers and workers exposed to high combustion PM levels contain mutagenic signatures derived from PAHs. However, recent findings suggest that ambient air PM(2.5) exposure primarily induces lung cancer development through tumor promotion of cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss the role of AhR and PAHs in lung cancer development caused by air pollution focusing on the tumor promoting properties including metabolism, immune system, cell proliferation and survival, tumor microenvironment, cell-to-cell communication, tumor growth and metastasis. We suggest that the dichotomy in lung cancer patterns observed between smoking and outdoor air PM(2.5) represent the two ends of a dose-response continuum of combustion PM exposure, where tumor promotion in the peripheral lung appears to be the driving factor at the relatively low-dose exposures from ambient air PM(2.5), whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.
2021
Hýžďalová, Martina; Procházková, Jiřina; Strapáčová, Simona; Svržková, Lucie; Vacek, Ondřej; Fedr, Radek; Andrysík, Zdeněk; Hrubá, Eva; Líbalová, Helena; Kléma, Jiří; Topinka, Jan; Mašek, Josef; Souček, Karel; Vondráček, Jan; Machala, Miroslav
In: Chemosphere, vol. 263, pp. 128126, 2021, ISSN: 1879-1298 0045-6535, (Place: England).
Abstract | Links | BibTeX | Tags: *Carcinoma, *Lung Neoplasms/genetics, Aryl Hydrocarbon/genetics, BaP, Benzo(a)pyrene/toxicity, Cell Proliferation, EMT, Epithelial Cells, Humans, Lung, Lung carcinoma, Phenotype, Receptors, TCDD, Tumor progression
@article{hyzdalova_prolonged_2021,
title = {A prolonged exposure of human lung carcinoma epithelial cells to benzo[a]pyrene induces p21-dependent epithelial-to-mesenchymal transition (EMT)-like phenotype.},
author = {Martina Hýžďalová and Jiřina Procházková and Simona Strapáčová and Lucie Svržková and Ondřej Vacek and Radek Fedr and Zdeněk Andrysík and Eva Hrubá and Helena Líbalová and Jiří Kléma and Jan Topinka and Josef Mašek and Karel Souček and Jan Vondráček and Miroslav Machala},
doi = {10.1016/j.chemosphere.2020.128126},
issn = {1879-1298 0045-6535},
year = {2021},
date = {2021-01-01},
journal = {Chemosphere},
volume = {263},
pages = {128126},
abstract = {Deciphering the role of the aryl hydrocarbon receptor (AhR) in lung cancer cells may help us to better understand the role of toxic AhR ligands in lung carcinogenesis, including cancer progression. We employed human lung carcinoma A549 cells to investigate their fate after continuous two-week exposure to model AhR agonists, genotoxic benzo[a]pyrene (BaP; 1 μM) and non-genotoxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 nM). While TCDD increased proliferative rate of A549 cells, exposure to BaP decreased cell proliferation and induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which was associated with enhanced cell migration, invasion, and altered cell morphology. Although TCDD also suppressed expression of E-cadherin and activated some genes linked to EMT, it did not induce the EMT-like phenotype. The results of transcriptomic analysis, and the opposite effects of BaP and TCDD on cell proliferation, indicated that a delay in cell cycle progression, together with a slight increase of senescence (when coupled with AhR activation), favors the induction of EMT-like phenotype. The shift towards EMT-like phenotype observed after simultaneous treatment with TCDD and mitomycin C (an inhibitor of cell proliferation) confirmed the hypothesis. Since BaP decreased cell proliferative rate via induction of p21 expression, we generated the A549 cell model with reduced p21 expression and exposed it to BaP for two weeks. The p21 knockdown suppressed the BaP-mediated EMT-like phenotype in A549 cells, thus confirming that a delayed cell cycle progression, together with p21-dependent induction of senescence-related chemokine CCL2, may contribute to induction of EMT-like cell phenotype in lung cells exposed to genotoxic AhR ligands.},
note = {Place: England},
keywords = {*Carcinoma, *Lung Neoplasms/genetics, Aryl Hydrocarbon/genetics, BaP, Benzo(a)pyrene/toxicity, Cell Proliferation, EMT, Epithelial Cells, Humans, Lung, Lung carcinoma, Phenotype, Receptors, TCDD, Tumor progression},
pubstate = {published},
tppubtype = {article}
}
Deciphering the role of the aryl hydrocarbon receptor (AhR) in lung cancer cells may help us to better understand the role of toxic AhR ligands in lung carcinogenesis, including cancer progression. We employed human lung carcinoma A549 cells to investigate their fate after continuous two-week exposure to model AhR agonists, genotoxic benzo[a]pyrene (BaP; 1 μM) and non-genotoxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 nM). While TCDD increased proliferative rate of A549 cells, exposure to BaP decreased cell proliferation and induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which was associated with enhanced cell migration, invasion, and altered cell morphology. Although TCDD also suppressed expression of E-cadherin and activated some genes linked to EMT, it did not induce the EMT-like phenotype. The results of transcriptomic analysis, and the opposite effects of BaP and TCDD on cell proliferation, indicated that a delay in cell cycle progression, together with a slight increase of senescence (when coupled with AhR activation), favors the induction of EMT-like phenotype. The shift towards EMT-like phenotype observed after simultaneous treatment with TCDD and mitomycin C (an inhibitor of cell proliferation) confirmed the hypothesis. Since BaP decreased cell proliferative rate via induction of p21 expression, we generated the A549 cell model with reduced p21 expression and exposed it to BaP for two weeks. The p21 knockdown suppressed the BaP-mediated EMT-like phenotype in A549 cells, thus confirming that a delayed cell cycle progression, together with p21-dependent induction of senescence-related chemokine CCL2, may contribute to induction of EMT-like cell phenotype in lung cells exposed to genotoxic AhR ligands.