Search Results (498)

Landfill tire fires are complex environmental disasters generating toxic pollutants with severe health risks. This study quantified emission dynamics and toxicological consequences of a large-scale tire fire in an urban ecosystem. A comprehensive source-to-receptor approach was applied, integrating Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) atmospheric dispersion modeling with comparison against air quality monitoring data. Soil samples collected from the fireground and surrounding urban allotment gardens were analyzed for tire-specific tracers (Zn) and 16 priority polycyclic aromatic hydrocarbons (PAHs). Human health risks were assessed using Incremental Lifetime Cancer Risk (ILCR), Toxic Equivalency Quotient (TEQ), and Mutagenic Equivalency Quotient (MEQ) metrics. Fire emissions were dominated by particulate matter (PM₁₀: 1.34 t) and PAHs (17.7 kg). Soil at the fire site showed severe contamination (Σ PAHs: 148.9 mg/kg), with benzo[a]pyrene as the primary carcinogen. The cumulative ILCR for children reached 9.7 × 10⁻⁴, exceeding the commonly used upper regulatory benchmark of 10⁻⁴. Dermal contact was identified as the dominant exposure pathway for pyrogenic PAHs. Elevated risk levels persisted at distal residential sites (ILCR: 10⁻⁵–10⁻⁴), indicating long-term environmental contamination Ecological risk quotients (RQ) exceeded unity for PAHs across all fire-impacted locations and for Zn and Cu in the immediate vicinity of the fire scene. These findings demonstrate that acute tire fire events can evolve into persistent terrestrial health hazards, highlighting the critical role of dermal exposure in PAH uptake and the need for long-term environmental monitoring and adaptive land-use management strategies to mitigate chronic health risks in urban populations. Full article

Introduction: Temperature is a key environmental factor influencing the physiological and biochemical processes of aquatic organisms, including xenobiotic metabolism. Understanding how temperature modulates the toxicological effects of pollutants such as polycyclic aromatic hydrocarbons (PAHs) is crucial in the context of climate change. Among these compounds, benzo[a]pyrene (BaP) and benzo[a]anthracene (BaA) are priority pollutants in aquatic environments, resulting from incomplete combustion. Their relevance is attributed to persistence and metabolic bioactivation potential. Fish primary hepatocyte cultures represent a relevant in vitro model for studying combined effects of thermal stress and chemical exposures, while supporting the 3Rs principles (Replacement, Reduction, and Refinement). Objective: This study aims to assess temperature-dependent effects of BaP and BaA, and their mixtures in brown trout hepatocytes using cytochrome P450 1A (CYP1A) immunohistochemistry as an indicator of xenobiotic metabolism. Methodology: Primary hepatocytes were isolated using a two-step collagenase perfusion method and cultured in 24-well plates at 18 °C and 22 °C. Cells were exposed for 72 h to supplemented L-15 medium (control) or to 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), as well as to single exposures of 1 and 10 µM of BaP and BaA and to equimolar mixtures of both compounds (1 and 10 µM). Viability was assessed using the lactate dehydrogenase (LDH) assay. CYP1A immunostaining was quantified based on cytoplasmic staining intensity relative to background area. Results: No significant effects on cell viability were observed under any condition. Temperature significantly reduced CYP1A expression in single exposures at 22 °C compared to 18 °C. BaP induced a significant dose-dependent increase, while BaA differed from controls only at 10 µM. In mixtures, only treatment- and dose-dependent effects were observed, with no temperature influence detected. Conclusions: Overall, the data highlight temperature as a key modulator of biochemical responses to PAHs, with single and mixed exposures eliciting distinct effects and suggesting potential synergism in mixtures. Full article

Endocrine-disrupting chemicals (EDCs) are important environmental risk factors for urogenital malignancies, but the shared molecular mechanisms underlying their carcinogenic effects remain poorly understood. Here, we systematically investigated the common pro-tumorigenic mechanisms of 12 prevalent EDCs, including anthracene, benzo[a]pyrene (BaP), bisphenol A, clofenotane, di(2-ethylhexyl) phthalate, diazinon, dibutyl phthalate, glyphosate, malathion, perfluorooctanoic acid, polychlorinated biphenyls, and triclosan, across four urogenital cancers, including bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). By integrating network toxicology and protein–protein interaction analysis, we identified shared hub targets linking EDC exposure to tumor progression. EGFR and CASP3 were identified as core targets in BLCA, EGFR and CASP9 in RCC, and CASP3, ESR1, and EGFR in PRAD, whereas KIT emerged as a broadly relevant target in TGCT. Molecular docking and molecular dynamics simulations supported the stable binding of EDCs to these targets. Among the predicted interactions, BaP showed strong binding affinity for CASP9 (ΔG = −9.8 kcal/mol) and was therefore selected for experimental validation. Analysis of TCGA data showed that elevated CASP9 expression was significantly associated with poorer overall survival in patients with RCC. In 786-O and ACHN cells, chronic exposure to an environmentally relevant concentration of BaP significantly increased CASP9 protein stability without altering its mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings identify shared molecular targets of EDCs across urogenital cancers and provide new mechanistic insight into EDC-driven tumor progression, prioritizing potential biomarkers and therapeutic targets for environmentally related malignancies. Full article

The ‘molecular mimicry theory’ states that foreign antigens introduced during infection can activate autoreactive T or B cells, leading to autoimmune diseases. However, despite a decrease in infectious burden, autoimmune disease incidence is on the rise globally. To address this paradox, we analyzed the impact of benzo[a]pyrene (BaP) on the autoimmune-prone mouse strain MRL. We found that BaP induced the expression of genes, the protein products of which showed homology to bacterial pathogens, in the MRL spleen and kidneys. Based on our findings, we propose the hypothesis that environmental pollutants may ‘mimic’ the impact of pathogen invasion on the immune system in autoimmune-susceptible individuals. Full article

Background/Objectives: Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by tumor-intrinsic and environmental resistance mechanisms. Benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon from tobacco smoke, combustion, and dietary sources, is a known carcinogen; however, its role in modulating therapeutic responses is poorly understood. Studies, including ours, implicate the platelet-activating factor-receptor (PAFR) pathway in mediating environmental pollutant and therapy-induced effects on tumor growth and microvesicle particle (MVP) release. We hypothesized that PAFR activation mediates BaP-induced NSCLC progression and influences EGFR-TKI responses. Methods: We assessed the effects of BaP, PAFR agonist CPAF, EGFR-TKIs, and their combinations on cell viability, proliferation, migration, anchorage-independent growth, and MVP secretion. Results: BaP did not alter cell survival but significantly increased migration, growth, colony formation, and MVP release, similar to CPAF, and these effects were blocked by a PAFR antagonist or acid sphingomyelinase inhibitor. Notably, BaP did not significantly reduce EGFR-TKI efficacy at tested concentrations. Conclusions: These results show that environmental carcinogens modulate NSCLC behavior through PAFR signaling without compromising EGFR-TKI responsiveness, highlighting PAFR as a potential therapeutic target. Full article

Background: Oil spills have dramatically increased, causing significant damage and pollution to marine ecosystems. The entry of petroleum hydrocarbons into the ocean may lead to the occurrence of harmful algal blooms (HABs). The amino acid changes in harmful algae after oil spills remain unclear. Methods: In order to study the effect of oil spills on the amino acid mechanism of typical causative species, the composition and relative abundance of amino acids in Heterosigma akashiwo were investigated under different water accommodated fractions (WAFs) of 180# fuel oil. Results: Random forest prediction of polycyclic aromatic hydrocarbon toxicity to microalgae identified pyrene, benzo[k]fluoranthene, and fluoranthene as significant contributors. A total of 16 species of amino acids were detected in Heterosigma akashiwo, among which alanine, proline, aspartic acid, cysteine, lysine, and histidine were the predominant ones. As the concentration of the WAF increased, alanine abundance decreased significantly, indicating that the WAF disrupted the metabolic balance of alanine, with the degree of interference being positively correlated with exposure concentration. With the increase in culture time, the abundance of cysteine increased at 1%, 3%, and 5% WAFs, whereas the cysteine increased and then decreased at 7% and 10% WAFs. The abundance of aspartic acid and lysine showed no obvious pattern with culture time under WAF stress. Significant increases in the abundance of proline and histidine were observed in the WAF treatments. Conclusions: This study investigated the impact of oil spill pressure on the amino acid content of harmful algae, providing a scientific basis for understanding the potential impact of oil spills on the occurrence of HABs. Full article

A three-year (January 2020–December 2022) daily dataset of 16 polycyclic aromatic hydrocarbons (PAHs) collected in parallel with PM_2.5 and a suite of meteorological variables at a coastal Mediterranean urban site in southern Italy (Pomigliano d’Arco, Campania) is presented and analysed. Raw PAH time series were decomposed into a long-term trend component (LT), a seasonal component (ST), and a residual component (RT) using an iterative missing-value-robust Kolmogorov–Zurbenko (KZ) moving-average filter. Spearman rank correlations between PAH concentrations and four meteorological predictors (mean temperature, relative humidity, mean wind speed, and maximum wind speed) were computed for each congener. Diagnostic molecular ratios—Fla/(Fla + Pyr), BaP/BghiP, Indeno[1,2,3-cd]pyrene/(IcdP + BghiP), and BaA/(BaA + Chr)—were evaluated seasonally and interpreted jointly with an information-theoretic Bayesian mixture modelling procedure (SNOB/MML) and with the documented susceptibility of some PAH ratios, especially BaP-containing ratios, to atmospheric ageing, phase repartitioning and summer photodegradation. Total PAH concentrations (sum of 16 congeners) ranged from <1 ng m⁻³ in summer to 46 ng m⁻³ during winter high-pollution episodes, with BaP peaking at ≈6.7 ng m⁻³. Because BaP was measured in the PM_2.5 fraction, comparisons with the EU annual target value of 1 ng m⁻³ established for PM₁₀-bound BaP are treated as indicative context only, not as formal compliance statements. Pronounced seasonal variability was driven primarily by residential heating emissions, and the incremental lifetime cancer risk (ILCR) for inhalation exposure reached $1.03\times {10}^{-4}$ (95% CI: $0.88$–$1.20\times {10}^{-4}$) during the heating season under a continuous outdoor-exposure worst-case scenario. The absolute ILCR magnitude is conditional on the selected TEF scheme and on the adopted BaP unit-risk coefficient; under an additional indoor-dominated scenario (16 h day⁻¹, infiltration factor 0.6), the corresponding risk remained above the conventional ${10}^{-6}$ benchmark. An anomalous near-background PAH signal during spring 2020 is attributed to the COVID-19 national lockdown, which reduced total PAH concentrations by approximately 85% relative to the seasonal component predicted by the iterative moving-average filter for the same calendar window. Source apportionment via diagnostic ratios identifies residential/biomass combustion as the dominant cold-season source and vehicular emissions as the prevailing warm-season source. These results provide a novel characterisation of PAH pollution dynamics in the undersampled southern Mediterranean and provide evidence to support targeted abatement policies. Full article

Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants formed during the incomplete combustion of organic material. Their persistence, bioaccumulation, and metabolic activation contribute to mutagenic and cytotoxic outcomes. Among these are benzo[a]pyrene (B[a]P), the most studied PAH and a benchmark compound for PAH carcinogenicity, and pyrene, a PAH whose urinary metabolite 1-hydroxypyrene is widely used as a biomarker of PAH exposure. B[a]P undergoes CYP1A1-mediated oxidation to generate reactive oxygen species (ROS) via epoxide and quinone redox cycling, whereas pyrene produces ROS primarily through pyrene-quinone redox cycling. We investigated cobinamide, a vitamin B₁₂/cobalamin analog with potent antioxidant properties, for mitigating benzo[a]pyrene- and pyrene-induced injury. In H9C2 rat embryonic cardiomyoblasts and A549 human lung epithelial cells exposed to B[a]P (10 μM) or pyrene (10–100 μM), cobinamide (5–10 μM) attenuated PAH-induced reductions in cell number in both models, while in H9C2 cells, it also attenuated decreases in metabolic activity and reduced apoptosis. Cobinamide also returned JNK/p38 phosphorylation to near baseline levels, decreased DNA and protein oxidation and DNA strand breaks. Transcriptionally, cobinamide suppressed inflammatory (TNF-α, IL-1β, and IL-6) and oxidative stress genes (HMOX1 and NOX4), while enhancing oxidative response (SOD2) and xenobiotic metabolism (CYP1A1). In Drosophila melanogaster exposed to 5 mM B[a]P/pyrene, 2 mM cobinamide improved survival and fully restored locomotion, outperforming cobalamin (minimal benefit) and N-acetylcysteine (partial rescue). Spectroscopic analyses showed no direct cobinamide-PAH binding. These findings demonstrate that cobinamide efficiently limits ROS-mediated PAH injury through redox modulation while preserving xenobiotic metabolism, suggesting its potential therapeutic use to mitigate PAH-induced toxicity. Full article

Uncontrolled scrap tire fires represent high-intensity episodic emission events that pose severe toxicological threats to urban environments. This study employs atmospheric dispersion modelling to quantify the impact of a tire stockpile fire on a distal educational receptor, evaluating two distinct dynamic stages of the event: an initial high-intensity open flame scenario (E1, 4 h) and a prolonged smouldering/suppression scenario (E2, 6 h), induced by firefighting interventions. Results reveal extreme pollutant loading at the receptor site during E1, with PM₁₀ and SO₂ concentrations peaking at 23,766 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$ and 7821 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$ respectively, indicating an immediate risk of acute respiratory distress. The organic fraction was dominated by volatile organic compounds (VOCs) (8691 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$) and a ∑16 PAHs flux of 313.9 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$. Toxicological assessment identified Benzo[a]pyrene (BaP) as the primary driver of health hazards, contributing approximately 70% to the carcinogenic risk profile. A critical disparity was observed between Mutagenic Equivalency (MEQ) of 18.32 and Toxic Equivalency (TEQ) of 15.37, suggesting that standard monitoring significantly underestimates the biological threat to sensitive paediatric populations. These findings demonstrate that acute, oxygen-limited tire combustion creates a concentrated toxic slug of high-molecular-weight PAHs. The study underscores the necessity of integrating mutagenicity-based models into emergency response protocols to accurately safeguard vulnerable communities against the long-term toxicological legacy of elastomer thermolysis. Full article

Particulate matter is a significant component of air pollutants, especially PM_2.5-bound polycyclic aromatic hydrocarbons (PAHs), due to multiple toxicological effects on organisms. In this study, the concentrations of PM_2.5-bound PAHs at the two most important ports in Mexico (Veracruz and Manzanillo) were determined to identify emission sources and evaluate potential health impacts. Average PM_2.5 concentrations were higher in Veracruz (12.90 ± 4.77 μg/m³) than in Manzanillo (10.96 ± 3.99 μg/m³), although both were below Mexico’s current air quality standards. Total PAH concentrations were also higher in Veracruz (22.14 ± 16.76 ng/m³) compared to Manzanillo (11.65 ± 9.04 ng/m³). The identified PAHs and diagnostic ratios indicated different emissions patterns: in Manzanillo, concentrations were associated with high-temperature pyrogenic sources, while in Veracruz, greater contributions from mixed sources were observed. The ILCR assessment was 4.61 × 10⁻⁷ for Manzanillo and 8.77 × 10⁻⁷ for Veracruz, both below the accepted risk threshold. Despite relatively low health risk estimates, the presence of carcinogenic PAHs, such as benzo[a]pyrene, highlights the need for continuous monitoring and mitigation strategies in port environments. These results provide pioneering, highly valuable insights into the dynamics of air pollution in these Mexican ports and their potential health implications. Full article

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are major risk factors for lung cancer and other diseases, acting through the aryl hydrocarbon receptor (AHR). Alveolar macrophages (AMs) help regulate the lung microenvironment by responding to inhaled toxicants and resident microbiota. Although small extracellular vesicles (sEVs, aka exosomes) released by AMs mediate intercellular communication and immune responses, the influence of lung microbiota on sEV biogenesis and the mechanisms underlying sEV dysregulation during PAH exposure remain unknown. Here, we investigated the interplay between AMs, B[a]P, and lung microbiota, focusing on sEV-associated miRNAs (exo-miRNAs). Murine AMs (MH-S) were exposed to varying B[a]P concentrations in the presence or absence of murine lung microbiota with or without an AHR antagonist. sEVs from each condition were characterized and profiled for miRNA. Distinct miRNA signatures emerged: high-dose B[a]P enriched miRNAs linked to cancer progression, whereas lung microbiota alone or with low-dose B[a]P induced tumor-suppressor miRNAs that limit proliferation and metastasis and promote apoptosis, an effect enhanced by AHR antagonism. Lung microbiota appeared to counteract high-dose B[a]P by modulating tumor-suppressive exo-miRNAs. This study demonstrates that lung microbiota-induced exo-miRNAs critically shape AM-derived sEV-miRNA signaling during PAH exposure. The identified exosomal miRNAs could serve as important exposure biomarkers and therapeutic targets for mitigating B[a]P-induced toxicity and cancer development. Full article

Polycyclic aromatic hydrocarbons (PAHs)-contaminated soils are often concomitantly polluted with heavy metals, which form combined contamination through cation–π interactions and other mechanisms. However, the mechanism by which bacteria degrade PAHs under combined pollution conditions remains insufficiently studied. In this study, a benzo[a]pyrene (BaP)-degrading bacterial strain, Rhodococcus sp. PDS1, was isolated from the co-contaminated soil of an abandoned coking plant in a steel factory. This strain can not only detoxify arsenic via reductive transformation, but also mediate extracellular arsenic oxidation and efficiently degrade BaP, a high-molecular-weight (HMW) polycyclic aromatic hydrocarbon with low bioavailability and high toxicity. Response surface methodology (RSM) experiments were conducted to optimize the degrading conditions of strain PDS1, considering four factors: pH, temperature, BaP concentration, and trivalent arsenic As(III) concentration. The results showed that the BaP removal by PDS1 would reach 93.59% under the RSM-obtained optimal conditions: pH 7.7, BaP concentration 8.96 mg/L, As(III) concentration 0.82 mM, and culture temperature 36.0 °C. The transcriptome of the strain under the combined stress of arsenic and BaP was further analyzed. The results indicated that the introduction of arsenic induced the upregulated expression of different genes in the arsenic detoxification ars operon and the pcaH/G gene (encoding protocatechuate 3,4-dioxygenase, a key enzyme in BaP degradation) to varying degrees. These findings clarify the mechanism of the degradation of HMW-PAHs such as BaP by strain PDS1 under PAHs–arsenic combined pollution, lay a solid theoretical foundation for subsequent practical applications, and demonstrate the broad prospects of strain PDS1 in the remediation of actual complex contaminated soils. Full article

Donor–acceptor (D-A)-type conjugated porous polymers (CPPs) have emerged as highly competitive photocatalysts for aerobic oxidation reactions. Herein, we rationally design and synthesize a series of D-A structured photocatalysts by employing dibenzothiophene-S, S-dioxide (BTDO) as the acceptor unit, and 4,8-bis(thiophen-2-yl) benzo [1,2-b:4,5-b’] dithiophene (DBD) and pyrene (Py) as the donor units. The effects of acceptor content on the optoelectronic and photocatalytic properties are systematically investigated. With the gradual increase in BTDO proportion and the decrease in pyrene content, the photocatalysts exhibit gradually narrowed band gaps, significantly promoted charge separation efficiency, and broadened visible light absorption range. Among the five as-prepared photocatalysts, DBD-T displays superior catalytic performance toward blue light-driven aerobic oxidation. Under mild conditions, benzyl sulfide and benzyl amine are selectively converted into benzyl sulfoxide and benzyl imine with a high conversion efficiency up to 96%. Moreover, DBD-T shows good universality toward a wide range of substrates, together with excellent recyclability and long-term stability. This work demonstrates that enhancing the electron-withdrawing capability of the acceptor unit represents a feasible and effective strategy to boost the photocatalytic performance of D-A-type conjugated polymers. Full article

Chronic exposure to benzo[a]pyrene (BaP), a Group 1 IARC carcinogen, is a major driver of lung carcinogenesis; however, how sustained subcytotoxic exposure reprograms bronchial epithelium toward preneoplastic states remains poorly defined. Here, we subjected BEAS-2B human bronchial epithelial cells to 12 weeks of continuous BaP at environmentally relevant concentrations (0.1 and 1.0 µM) and interrogated the resulting phenotypes using an integrated multi-scale framework encompassing functional toxicology, RT-qPCR, RNA-seq, phospho-kinase/NF-κB arrays, and organotypic air–liquid interface (ALI) cultures. Cells maintained metabolic competence throughout, evidenced by sustained CYP1A1 and CYP1B1 induction at both acute (4 h) and chronic (12-week) timepoints, while accumulating genotoxic stress as demonstrated by dose-dependent nuclear γ-H2AX foci formation and ATM phosphorylation (Ser1981). RNA-seq revealed a dose-dependent transcriptional shift: 0.1 µM BaP yielded 119 differentially expressed genes (DEGs; |log2FC| ≥ 1, FDR < 0.05), whereas 1.0 µM generated 255 DEGs. Downregulated transcripts were enriched for extracellular matrix and cell-adhesion programs (COL14A1, ADAMTS2, CSMD3, CADM3), while upregulated genes encompassed inflammatory, calcium-signaling, and vesicle-trafficking modules (NFATC4, CSF2RA, SYT1, PCLO). Phospho-kinase/NF-κB arrays confirmed a p53/NF-κB signaling nexus, with concurrent activation of MAPK/ERK (Thr202/Tyr204) and PI3K/Akt (Ser473) pathways. Despite persistent genotoxic stress, cells did not acquire anchorage-independent growth and remained non-tumorigenic in vivo. Critically, ALI organotypic cultures derived from BaP-exposed cells exhibited histological dysplasia, nuclear pleomorphism, and disrupted apical-basal polarity. These findings mechanistically link chronic BaP exposure to an initiation-like preneoplastic state and establish a validated 2D/3D multi-omics platform for PAH-driven lung carcinogenesis research. Full article

Influenza A virus (IAV) remains a major global health threat, and host-directed antivirals may help overcome rapid viral mutation and drug resistance. Here, we performed a genome-wide siRNA screen in A549 cells using cell viability as an integrated endpoint to identify host determinants of IAV (PR8/H1N1) infection. Using plate-normalized viability ratios, we identified 2134 genes with >40% viability change after infection (2048 UP and 86 DOWN; two-tailed t-test, n = 3; p < 0.05, FDR < 0.1). MetaCore pathway analysis showed enrichment of programs linked to host response and tissue injury control, including RAS-related signaling and multiple metabolic pathways such as estradiol, ubiquinone/mitochondrial redox, and benzo[a]pyrene/xenobiotic metabolism. DAVID Gene Ontology analysis further highlighted biological processes relevant to infection, including endocytosis, transcription, and translation, consistent with host pathways supporting viral replication. Benchmarking against meta-analyzed RNAi and CRISPR resources revealed that shared hits were enriched for translation, nucleocytoplasmic transport, and ER-Golgi trafficking, supporting external validity, whereas the large unique UP fraction was dominated by hormone metabolism, detoxification, and mitochondrial redox/CoQ pathways, consistent with viability-specific, tolerance-associated host response programs. Integrating the screen with DrugBank identified 174 druggable host genes corresponding to 345 candidate compounds. Together, these findings provide a systematic resource of host factors influencing H1N1 infection, improve understanding of influenza virus–host interactions, and offer a foundation for future development of host-directed antiviral strategies and drug repurposing efforts. Full article