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.
2011
Varel, Urte Lübcke-von; Machala, Miroslav; Ciganek, Miroslav; Neca, Jiri; Pencikova, Katerina; Palkova, Lenka; Vondracek, Jan; Löffler, Ivonne; Streck, Georg; Reifferscheid, Georg; Flückiger-Isler, Sini; Weiss, Jana M.; Lamoree, Marja; Brack, Werner
Polar compounds dominate in vitro effects of sediment extracts. Journal Article
In: Environmental science & technology, vol. 45, no. 6, pp. 2384–2390, 2011, ISSN: 1520-5851 0013-936X, (Place: United States).
Abstract | Links | BibTeX | Tags: Animals, Aryl Hydrocarbon/analysis/chemistry, Biological Assay, Chemical Fractionation, Chemical/*analysis/chemistry/toxicity, Endocrine Disruptors/analysis/chemistry/toxicity, Environmental Monitoring, Geologic Sediments/*chemistry, Germany, Humans, Mutagens/analysis/chemistry/toxicity, Prealbumin/analysis/chemistry, Rats, Receptors, Toxicity Tests, Water Pollutants
@article{lubcke-von_varel_polar_2011,
title = {Polar compounds dominate in vitro effects of sediment extracts.},
author = {Urte Lübcke-von Varel and Miroslav Machala and Miroslav Ciganek and Jiri Neca and Katerina Pencikova and Lenka Palkova and Jan Vondracek and Ivonne Löffler and Georg Streck and Georg Reifferscheid and Sini Flückiger-Isler and Jana M. Weiss and Marja Lamoree and Werner Brack},
doi = {10.1021/es103381y},
issn = {1520-5851 0013-936X},
year = {2011},
date = {2011-03-01},
journal = {Environmental science & technology},
volume = {45},
number = {6},
pages = {2384–2390},
abstract = {Sediment extracts from three polluted sites of the river Elbe basin were fractionated using a novel online fractionation procedure. Resulting fractions were screened for mutagenic, aryl hydrocarbon receptor (AhR)-mediated, transthyretin (TTR)-binding, and estrogenic activities and their potency to inhibit gap junctional intercellular communication (GJIC) to compare toxicity patterns and identify priority fractions. Additionally, more than 200 compounds and compound classes were identified using GC-MS/MS, LC-MS/MS, and HPLC-DAD methods. For all investigated end points, major activities were found in polar fractions, which are defined here as fractions containing dominantly compounds with at least one polar functional group. Nonpolar PAH fractions contributed to mutagenic and AhR-mediated activities while inhibition of GJIC and estrogenic and TTR-binding activities were exclusively observed in the polar fractions. Known mutagens in polar fractions included nitro- and dinitro-PAHs, azaarenes, and keto-PAHs, while parent and monomethylated PAHs such as benzo[a]pyrene and benzofluoranthenes were identified in nonpolar fractions. Additionally, for one sample, high AhR-mediated activities were determined in one fraction characterized by PCDD/Fs, PCBs, and PCNs. Estrone, 17β-estradiol, 9H-benz[de]anthracen-7-one, and 4-nonylphenol were identified as possible estrogenic and TTR-binding compounds. Thus, not only nonpolar compounds such as PAHs, PCBs, and PCDD/Fs but also the less characterized and investigated more polar substances should be considered as potent mutagenic, estrogenic, AhR-inducing, TTR-binding, and GJIC-inhibiting components for future studies.},
note = {Place: United States},
keywords = {Animals, Aryl Hydrocarbon/analysis/chemistry, Biological Assay, Chemical Fractionation, Chemical/*analysis/chemistry/toxicity, Endocrine Disruptors/analysis/chemistry/toxicity, Environmental Monitoring, Geologic Sediments/*chemistry, Germany, Humans, Mutagens/analysis/chemistry/toxicity, Prealbumin/analysis/chemistry, Rats, Receptors, Toxicity Tests, Water Pollutants},
pubstate = {published},
tppubtype = {article}
}
Sediment extracts from three polluted sites of the river Elbe basin were fractionated using a novel online fractionation procedure. Resulting fractions were screened for mutagenic, aryl hydrocarbon receptor (AhR)-mediated, transthyretin (TTR)-binding, and estrogenic activities and their potency to inhibit gap junctional intercellular communication (GJIC) to compare toxicity patterns and identify priority fractions. Additionally, more than 200 compounds and compound classes were identified using GC-MS/MS, LC-MS/MS, and HPLC-DAD methods. For all investigated end points, major activities were found in polar fractions, which are defined here as fractions containing dominantly compounds with at least one polar functional group. Nonpolar PAH fractions contributed to mutagenic and AhR-mediated activities while inhibition of GJIC and estrogenic and TTR-binding activities were exclusively observed in the polar fractions. Known mutagens in polar fractions included nitro- and dinitro-PAHs, azaarenes, and keto-PAHs, while parent and monomethylated PAHs such as benzo[a]pyrene and benzofluoranthenes were identified in nonpolar fractions. Additionally, for one sample, high AhR-mediated activities were determined in one fraction characterized by PCDD/Fs, PCBs, and PCNs. Estrone, 17β-estradiol, 9H-benz[de]anthracen-7-one, and 4-nonylphenol were identified as possible estrogenic and TTR-binding compounds. Thus, not only nonpolar compounds such as PAHs, PCBs, and PCDD/Fs but also the less characterized and investigated more polar substances should be considered as potent mutagenic, estrogenic, AhR-inducing, TTR-binding, and GJIC-inhibiting components for future studies.