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 (PM2.5), 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 PM2.5 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 PM2.5 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 PM2.5, whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.

• Keywords
• Air pollution, Carcinogenesis, Diesel exhaust, Genotoxicity, Inflammation, Occupational exposure, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion,
• MeSH
• Air Pollutants * toxicity   MeSH
• Humans MeSH
• Environmental Monitoring MeSH
• Tumor Microenvironment MeSH
• Lung Neoplasms * chemically induced   genetics   MeSH
• Particulate Matter toxicity   MeSH
• Polycyclic Aromatic Hydrocarbons * toxicity   MeSH
• Receptors, Aryl Hydrocarbon genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Air Pollutants * MeSH
• Particulate Matter MeSH
• Polycyclic Aromatic Hydrocarbons * MeSH
• Receptors, Aryl Hydrocarbon MeSH

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted great interest in novel broad-spectrum antivirals, including perylene-related compounds. In the present study, we performed a structure-activity relationship analysis of a series of perylene derivatives, which comprised a large planar perylene residue, and structurally divergent polar groups connected to the perylene core by a rigid ethynyl or thiophene linker. Most of the tested compounds did not exhibit significant cytotoxicity towards multiple cell types susceptible to SARS-CoV-2 infection, and did not change the expressions of cellular stress-related genes under normal light conditions. These compounds showed nanomolar or sub-micromolar dose-dependent anti-SARS-CoV-2 activity, and also suppressed the in vitro replication of feline coronavirus (FCoV), also termed feline infectious peritonitis virus (FIPV). Perylene compounds exhibited high affinity for liposomal and cellular membranes, and efficiently intercalated into the envelopes of SARS-CoV-2 virions, thereby blocking the viral-cell fusion machinery. Furthermore, the studied compounds were demonstrated to be potent photosensitizers, generating reactive oxygen species (ROS), and their anti-SARS-CoV-2 activities were considerably enhanced after irradiation with blue light. Our results indicated that photosensitization is the major mechanism underlying the anti-SARS-CoV-2 activity of perylene derivatives, with these compounds completely losing their antiviral potency under red light. Overall, perylene-based compounds are broad-spectrum antivirals against multiple enveloped viruses, with antiviral action based on light-induced photochemical damage (ROS-mediated, likely singlet oxygen-mediated), causing impairment of viral membrane rheology.

• Keywords
• Antiviral activity, Liposome, Membrane, Perylene-related compound, Photodynamic inactivation, SARS-CoV-2,
• MeSH
• Antiviral Agents pharmacology   chemistry   MeSH
• COVID-19 * MeSH
• Cats MeSH
• Perylene * pharmacology   MeSH
• Reactive Oxygen Species MeSH
• SARS-CoV-2 MeSH
• Singlet Oxygen MeSH
• Virion MeSH
• Viral Envelope MeSH
• Animals MeSH
• Check Tag
• Cats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antiviral Agents MeSH
• Perylene * MeSH
• Reactive Oxygen Species MeSH
• Singlet Oxygen MeSH

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzo[a]pyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhRKO cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaP-induced S-phase transition/cell proliferation were inhibited in MCF-7 AhRKO cells, whereas these cells remained sensitive towards both endogenous estrogen 17β-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhRKO cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benz[a]anthracene or 3-methylcholanthrene, were diminished in MCF-7 AhRKO cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolism of PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.

• MeSH
• Cell Culture Techniques MeSH
• Cell Cycle drug effects   genetics   MeSH
• Cytochrome P-450 CYP1A1 genetics   metabolism   MeSH
• Cytochrome P-450 CYP1B1 genetics   metabolism   MeSH
• Endocrine Disruptors metabolism   toxicity   MeSH
• Gene Expression drug effects   MeSH
• Genetic Vectors MeSH
• Gene Knockdown Techniques MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Plasmids MeSH
• Polycyclic Aromatic Hydrocarbons metabolism   toxicity   MeSH
• Cell Proliferation drug effects   genetics   MeSH
• Receptors, Aryl Hydrocarbon genetics   metabolism   MeSH
• Receptors, Estrogen genetics   metabolism   MeSH
• Genes, Reporter MeSH
• Transfection MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CYP1A1 protein, human MeSH Browser
• CYP1B1 protein, human MeSH Browser
• Cytochrome P-450 CYP1A1 MeSH
• Cytochrome P-450 CYP1B1 MeSH
• Endocrine Disruptors MeSH
• Polycyclic Aromatic Hydrocarbons MeSH
• Receptors, Aryl Hydrocarbon MeSH
• Receptors, Estrogen MeSH

This work aimed to determine the seasonal variations of polycyclic aromatic hydrocarbons (PAHs) in airborne PM10 at two background sites (Masná-MS, Líšeň-LN) in Brno over a 5-year period (2009-2013). Samples were collected on quartz filters using a low-volume sampler by continual filtration. Concentrations of PAHs in collected PM10 samples were determined using a gas chromatography with a mass spectrometer as a detector. A different number of PAHs were determined to be at each site, i.e., 11 PAHs at the MS site and six PAHs at the LN site, and similarities between them were identified using non-parametric analysis of variance. Potential sources were identified using principal component analysis (PCA) and PAHs diagnostic ratios. The work also focused on health risk assessment. This was estimated using toxic equivalent factors to calculate individual lifetime cancer risk, which quantifies risk of exposure to PAHs for specific age groups. The average 11-PAH concentrations in M|S site annually ranged from 19.28 ± 19.02 ng m-3 (2011) to 40.37 ± 21.35 ng m-3 (2013). With regard to the LN site, the average six-PAH concentrations annually ranged from 3.64 ± 3.87 ng m-3 (2009) and 5.27 ± 6.19 ng m-3 (2012). PCA and diagnostic ratios indicate the main sources to be traffic emissions and coal combustion. Health risk assessment showed carcinogenic risk under limit value in all cases.

• Keywords
• Factor analysis, Health risk, Particulate matter, Polycyclic aromatic hydrocarbons, Traffic emissions,
• MeSH
• Environmental Health MeSH
• Risk Assessment MeSH
• Air Pollutants * analysis   toxicity   MeSH
• Humans MeSH
• Environmental Monitoring methods   MeSH
• Polycyclic Aromatic Hydrocarbons * analysis   toxicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Air Pollutants * MeSH
• Polycyclic Aromatic Hydrocarbons * MeSH

Although passive sampling has been previously used for the monitoring of volatile and semi-volatile contaminants in air, there are limited data on the use of this technique coupled with bioassays based on specific biological responses. Biological responses including those mediated by the aryl hydrocarbon (AhR) receptor as well as (anti-)estrogenicity and (anti-)androgenicity of samples from four Eastern European countries (Lithuania, Slovakia, Romania, and Serbia) were determined. To address the potential differences of specific toxic potencies of pollutant mixtures in ambient air in Eastern Europe, each country was characterized by a single more remote location that served to determine regional background conditions and one location in more urbanized and industrialized locations, which were defined as "impacted" areas. Besides samples from Lithuania, a significant gradient in concentrations of AhR-mediated potency from background and impacted localities was observed. Greatest potencies were measured in samples from impacted locations in Romania and Slovakia. Concentrations of polycyclic aromatic hydrocarbons (PAHs) that were quantified accounted for 3-33 % of the 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents determined by use of the bioassay. No significant estrogenic potency was detected but anti-estrogenic effects were produced by air from two background locations (Lithuania, Slovakia) and three impacted locations (Lithuania, Romania, and Serbia). Anti-androgenic potency was observed in all samples. The greatest anti-estrogenic potency was observed at the background location in Slovakia. Anti-estrogenic and anti-androgenic potencies of studied air samples were probably associated with compounds that are not routinely monitored. The study documents suitability of passive air sampling for the assessment of specific toxic potencies of ambient air pollutants.

• MeSH
• Estrogens analysis   MeSH
• Air Pollutants analysis   MeSH
• Environmental Monitoring methods   MeSH
• Polychlorinated Dibenzodioxins analysis   MeSH
• Polycyclic Aromatic Hydrocarbons analysis   MeSH
• Receptors, Aryl Hydrocarbon MeSH
• Air Pollution statistics & numerical data   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe, Eastern MeSH
• Names of Substances
• Estrogens MeSH
• Air Pollutants MeSH
• Polychlorinated Dibenzodioxins MeSH
• Polycyclic Aromatic Hydrocarbons MeSH
• Receptors, Aryl Hydrocarbon MeSH

Changes in pollutant loads in relatively dynamic river sediments, which contain very complex mixtures of compounds, can play a crucial role in the fate and effects of pollutants in fluvial ecosystems. The contamination of sediments by bioactive substances can be sensitively assessed by in vitro bioassays. This is the first study that characterizes detailed short- and long-term changes in concentrations of contaminants with several modes of action in river sediments. One-year long monthly study described seasonal and spatial variability of contamination of sediments in a representative industrialized area by dioxin-like and endocrine disruptive chemicals. There were significant seasonal changes in both antiandrogenic and androgenic as well as dioxin-like potential of river sediments, while there were no general seasonal trends in estrogenicity. Aryl hydrocarbon receptor-dependent potency (dioxin-like potency) expressed as biological TCDD-equivalents (BIOTEQ) was in the range of 0.5-17.7 ng/g, dry mass (dm). The greatest BIOTEQ levels in sediments were observed during winter, particularly at locations downstream of the industrial area. Estrogenicity expressed as estradiol equivalents (EEQ) was in the range of 0.02-3.8 ng/g, dm. Antiandrogenicity was detected in all samples, while androgenic potency in the range of 0.7-16.8 ng/g, dm dihydrotestosterone equivalents (DHT-EQ) was found in only 30 % of samples, most often during autumn, when antiandrogenicity was the least. PAHs were predominant contaminants among analyzed pollutants, responsible, on average, for 13-21 % of BIOTEQ. Longer-term changes in concentrations of BIOTEQ corresponded to seasonal fluctuations, whereas for EEQ, the inter-annual changes at some locations were greater than seasonal variability during 1 year. The inter- as well as intra-annual variability in concentrations of both BIOTEQ and EEQ at individual sites was greater in spring than in autumn which was related to hydrological conditions in the river. This study stresses the importance of river hydrology and its seasonal variations in the design of effective sampling campaigns, as well as in the interpretation of any monitoring results.

• MeSH
• Biological Assay MeSH
• Water Pollutants, Chemical analysis   MeSH
• Water Pollution, Chemical statistics & numerical data   MeSH
• Dioxins analysis   MeSH
• Endocrine Disruptors analysis   MeSH
• Geologic Sediments chemistry   MeSH
• Environmental Monitoring * MeSH
• Polychlorinated Dibenzodioxins analysis   MeSH
• Polycyclic Aromatic Hydrocarbons analysis   MeSH
• Receptors, Aryl Hydrocarbon MeSH
• Rivers chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Water Pollutants, Chemical MeSH
• Dioxins MeSH
• Endocrine Disruptors MeSH
• Polychlorinated Dibenzodioxins MeSH
• Polycyclic Aromatic Hydrocarbons MeSH
• Receptors, Aryl Hydrocarbon MeSH

Chemicals in air were characterized for potential interference with signaling of estrogen, androgen, and arylhydrocarbon (AhR) receptors, which are known to play an important role in endocrine-disruptive changes in vivo. Previously, effects of this type have been studied mainly in particulate matter in the ambient air from various localities. In this study, both volatile and particulate fractions of air from three sites in Banja Luka region (Bosnia and Herzegovina) were investigated to describe the distribution of endocrine-disrupting contaminants on a small spatial scale. Circadian variability of air pollution was investigated by collecting samples during both day and night. Air samples collected from urban localities at night were more potent in producing the AhR-mediated effects than those collected during daytime. This trend was not observed at the reference rural location. None of the samples showed significant estrogenic or androgenic activity. On the other hand, anti-androgenicity was detected in both particulate and vapor phases, while anti-estrogenicity was detected only in the particulate fraction of air from all localities. The AhR-mediated potencies of samples were associated primarily with non-persistent compounds. Based on the concentrations of 28 individual compounds, PAHs accounted for approximately 30 % of the AhR-mediated potency determined by the bioassay. The results show that there can be a significant difference between levels of bioactive compounds in air between daytime and nighttime.

• MeSH
• Principal Component Analysis MeSH
• Receptors, Androgen MeSH
• Biological Assay MeSH
• Circadian Rhythm MeSH
• Endocrine Disruptors MeSH
• Rats MeSH
• Air Pollutants chemistry   MeSH
• Cell Line, Tumor MeSH
• Particulate Matter chemistry   MeSH
• Receptors, Estrogen MeSH
• Signal Transduction MeSH
• Volatile Organic Compounds chemistry   MeSH
• Air analysis   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Receptors, Androgen MeSH
• Endocrine Disruptors MeSH
• Air Pollutants MeSH
• Particulate Matter MeSH
• Receptors, Estrogen MeSH
• Volatile Organic Compounds MeSH