Frontiers in Toxicology

Our medical research library holds 8 studies published in Frontiers in Toxicology (2021–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Frontiers Research Foundation
• Published: 2019 to the present, Switzerland
• Language: English
• ISSN: 2673-3080 (electronic)
• Its record in the NLM Catalog

2020s

• Evaluating the QEAS-7 questionnaire as a predictor of asbestos burden in lung tissue among lung cancer patients: insights from the AMCANES study. G. Granados, A. Ferreiro, C. Gómez-Ollés, et al. 2026;8:1733214. PubMed · Publisher · Free full text

  Abstract

  Objectives: Asbestos exposure is a known risk factor for lung cancer, and quantifying asbestos bodies (ABs) in lung tissue remains the gold standard for assessing cumulative exposure. However, histological analysis is not routinely available in many clinical settings. The validated QEAS-7 questionnaire was developed to evaluate occupational, domestic, and environmental asbestos exposure. This study examined the association between QEAS-7 exposure classifications and the asbestos burden in lung cancer patients.

  Methods: A cross-sectional multicenter study was conducted across nine Spanish hospitals. Patients with histologically confirmed lung cancer undergoing surgical resection completed the QEAS-7 questionnaire. Non-tumoral lung tissue samples were analyzed for Abs and asbestos burden was categorized according to AB concentration (with elevated burden defined as >1000 AB/g). Diagnostic performance metrics were evaluated.

  Results: Among 133 patients (median age 67 years; 77% male), ABs were detected in 61% of samples, with 5% showing an elevated asbestos burden (>1000 AB/g). Occupational exposure was reported by 36% of patients and accounted for 71.4% of cases with elevated burden. Domestic exposure was reported by 9% of patients and detected in 28.6% of elevated-burden cases. The combined occupational and domestic exposure domain achieved 100% sensitivity for detecting elevated asbestos burden, while occupational and domestic domains alone showed sensitivities of 71.4% and 28.6%, respectively. Specificity and positive predictive values remained modest. Notably, 29% of patients classified as 'non-exposed' by QEAS-7 had measurable ABs.

  Conclusion: The QEAS-7 questionnaire demonstrated high sensitivity for detecting elevated asbestos burden when combining occupational and domestic exposures. While histological analysis remains the definitive method, QEAS-7 offers a practical screening alternative, when lacking access to tissue-based diagnostics or occupational hygiene expertise.

  Copyright © 2026 Granados, Ferreiro, Gómez-Ollés, González-Barcala, Navarro, Costa, Romero, Marín, Barroso, Urrutia, Dorado-Arenas, Uranga Echeverría, Marín, Garcia, Calero, Martín-Bustamante, Márquez, Cruz and Ferrer.

• Critical values for dimensional parameters of mesotheliomagenic mineral fibers: evidence from the dimensions and rigidity of MWCNT. A.G. Wylie, A.A. Korchevskiy. 2025;7:1568513. PubMed · Publisher · Free full text

  Abstract

  MWCNT (multi-walled carbon nanotubes) used in 72 animal instillation or inhalation studies were classified by average length, average width, Young's modulus, Rigidity Index (RI), and potency for mesothelioma in animals. The RI is based on the Euler buckling theory. MWCNT that induce mesothelioma have average lengths >2 µm and widths >37 nm, and average RI > 0.05 (µm2 x GPa x 104). Many noncarcinogenic MWCNT materials have RI < 0.05 and lack biological rigidity. In comparison, Elongate Mineral Particle (EMP) populations with one exception have RI > 0.05. Mineral particles likely to have RI < 0.05 include chrysotile fibrils with lengths >5 μm, amosite and crocidolite fibers with widths <60 nm, and sheet silicate fibers with widths <200 nm. The product of percent EMPA, average RI, and biosolubility among silicates correlates with known mesothelioma potency. The derived models reproduce published values of RM with high statistical significance (P < 0.05). Average RI, length, and width are critical parameters for mesotheliomagenicity for both MWCNT and EMPA mineral fiber.

  Copyright © 2025 Wylie and Korchevskiy.

• Editorial: Asbestos and disease genomics: is mesothelioma a genomic paradigm?. M.C. Jaurand, F. Murphy, E. Felley-Bosco. 2024;6:1536344. Editorial PubMed · Publisher · Free full text

• The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop. S.A. Fisher, K. Patrick, T. Hoang, et al. 2024;6:1373003. PubMed · Publisher · Free full text

  Abstract

  Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model. Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets. Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets. Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.

  Copyright © 2024 Fisher, Patrick, Hoang, Marcq, Behrouzfar, Young, Miller, Robinson, Bueno, Nowak, Lesterhuis, Morahan and Lake.

• Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma. P. Farahmand, K. Gyuraszova, C. Rooney, et al. 2023;5:1200650. PubMed · Publisher · Free full text

  Abstract

  Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit.

  Copyright © 2023 Farahmand, Gyuraszova, Rooney, Raffo-Iraolagoitia, Jayasekera, Hedley, Johnson, Chernova, Malviya, Hall, Monteverde, Blyth, Duffin, Carlin, Lewis, Le Quesne, MacFarlane and Murphy.

• NF2 alteration in mesothelioma. Y. Sekido, T. Sato. 2023;5:1161995. Review PubMed · Publisher · Free full text

  Abstract

  The NF2 tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%-40% mesotheliomas showing NF2 inactivation. NF2 encodes merlin, a member of the ezrin, radixin, and moesin (ERM) family of proteins that regulate cytoskeleton and cell signaling. Recent genome analysis revealed that NF2 alteration may be a late event in mesothelioma development, suggesting that NF2 mutation confers a more aggressive phenotype to mesothelioma cells and may not be directly caused by asbestos exposure. The Hippo tumor-suppressive and mTOR prooncogenic signaling pathways are crucial cell-signaling cascades regulated by merlin. Although the exact role and timing of NF2 inactivation in mesothelioma cells remain to be elucidated, targeting the NF2/merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.

  Copyright © 2023 Sekido and Sato.

• A Low-Serum Culture System for Prolonged in Vitro Toxicology Experiments on a Macrophage System. B. Dalzon, A. Torres, J. Devcic, et al. 2021;3:780778. Review PubMed · Publisher · Free full text

  Abstract

  Immunotoxicology sensu lato comprises not only toxicity toward immune cells, but also biological reactions from immune cells exposed to toxicants, reactions that may have deleterious effects at the organismal level. Within this wide frame, a specific case of interest is represented by the response of macrophages to particulate materials, with the epitome examples of asbestos and crystalline silica. For such toxicants that are both persistent and often encountered in an occupational setting, i.e. at low but repeated doses, there is a need for in vitro systems that can take into account these two parameters. Currently, most in vitro systems are used in an acute exposure mode, i.e., with a single dose and a readout made shortly if not immediately after exposure. We describe here how adequate changes of the culture methods applied to the murine macrophage cell line J774A.1 enable longer periods of culture (several days), which represents a first opportunity to address the persistence and dose-rate issues. To respond to this, the protocol uses a reduction in the concentration of the animal serum used for cell culture, as well as a switch from fetal to adult serum, which is less rich in proliferation factors. By doing so, we have considerably reduced cell proliferation, which is a problem with cell lines when they are supposed to represent slowly-dividing cells such as resident macrophages. We also succeeded in maintaining the differentiated functions of macrophages, such as phagocytosis or inflammatory responses, over the whole culture period. Furthermore, the presence of serum, even at low concentrations, provides excellent cell viability and keeps the presence of a protein corona on particulate materials, a feature that is known to strongly modulate their effects on cells and is lost in serum-free culture. Besides data showing the impact of these conditions on macrophages cell line cultures, illustrative examples are shown on silica- and cobalt-based pigments.

  Copyright © 2021 Dalzon, Torres, Devcic, Fenel, Sergent and Rabilloud.

• Centrality of Myeloid-Lineage Phagocytes in Particle-Triggered Inflammation and Autoimmunity. O.K. Favor, J.J. Pestka, M.A. Bates, et al. 2021;3:777768. Review PubMed · Publisher · Free full text

  Abstract

  Exposure to exogenous particles found as airborne contaminants or endogenous particles that form by crystallization of certain nutrients can activate inflammatory pathways and potentially accelerate autoimmunity onset and progression in genetically predisposed individuals. The first line of innate immunological defense against particles are myeloid-lineage phagocytes, namely macrophages and neutrophils, which recognize/internalize the particles, release inflammatory mediators, undergo programmed/unprogrammed death, and recruit/activate other leukocytes to clear the particles and resolve inflammation. However, immunogenic cell death and release of damage-associated molecules, collectively referred to as "danger signals," coupled with failure to efficiently clear dead/dying cells, can elicit unresolved inflammation, accumulation of self-antigens, and adaptive leukocyte recruitment/activation. Collectively, these events can promote loss of immunological self-tolerance and onset/progression of autoimmunity. This review discusses critical molecular mechanisms by which exogenous particles (i.e., silica, asbestos, carbon nanotubes, titanium dioxide, aluminum-containing salts) and endogenous particles (i.e., monosodium urate, cholesterol crystals, calcium-containing salts) may promote unresolved inflammation and autoimmunity by inducing toxic responses in myeloid-lineage phagocytes with emphases on inflammasome activation and necrotic and programmed cell death pathways. A prototypical example is occupational exposure to respirable crystalline silica, which is etiologically linked to systemic lupus erythematosus (SLE) and other human autoimmune diseases. Importantly, airway instillation of SLE-prone mice with crystalline silica elicits severe pulmonary pathology involving accumulation of particle-laden alveolar macrophages, dying and dead cells, nuclear and cytoplasmic debris, and neutrophilic inflammation that drive cytokine, chemokine, and interferon-regulated gene expression. Silica-induced immunogenic cell death and danger signal release triggers accumulation of T and B cells, along with IgG-secreting plasma cells, indicative of ectopic lymphoid tissue neogenesis, and broad-spectrum autoantibody production in the lung. These events drive early autoimmunity onset and accelerate end-stage autoimmune glomerulonephritis. Intriguingly, dietary supplementation with ω-3 fatty acids have been demonstrated to be an intervention against silica-triggered murine autoimmunity. Taken together, further insight into how particles drive immunogenic cell death and danger signaling in myeloid-lineage phagocytes and how these responses are influenced by the genome will be essential for identification of novel interventions for preventing and treating inflammatory and autoimmune diseases associated with these agents.

  Copyright © 2021 Favor, Pestka, Bates and Lee.

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