Molecular Mechanisms of the Toxicity and Carcinogenicity of Particulates

Topic Information

Dear Colleagues,

We are pleased to inform you that we are planning a Topic on the molecular mechanisms of the toxicity and carcinogenicity of particulates. Particles and fibers affect human health as a function of their physicochemical properties, but both the mechanisms of action and link between physicochemical features and adverse responses are still often unclear. Knowledge of these mechanisms is fundamental for hazard identification and the development of new testing approaches as well as safe-by-design practices. This Topic aims to increase knowledge about the mechanisms of toxicity and role of physicochemical properties in the induction of adverse responses. Given your expertise in the field, we would like to invite you to send us a contribution. Original research articles (in vitro and in vivo studies) and reviews are welcome. Research areas may include (but are not limited to) particles and fibers of natural origin (asbestos and fibrous minerals, silica, volcanic ashes, and celestial dusts) and anthropic origin (artificial fibers, carbon nanotubes, titanium dioxide, particulate matter, metals, etc.), as well as the nanoparticles comprising them. We look forward to receiving your contributions.

Dr. Maura Tomatis
Dr. Elisabetta Aldieri
Topic Editors

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biology biology	3.6	5.7	2012	16.4 Days	CHF 2700
Cancers cancers	4.5	8.0	2009	17.4 Days	CHF 2900
Healthcare healthcare	2.4	3.5	2013	20.3 Days	CHF 2700
Onco onco	-	-	2021	27.8 Days	CHF 1000
Pathophysiology pathophysiology	2.7	3.1	1994	30.7 Days	CHF 1400
Toxics toxics	3.9	4.5	2013	18.3 Days	CHF 2600
Biomolecules biomolecules	4.8	9.4	2011	18.4 Days	CHF 2700
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900

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Published Papers (3 papers)

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All Biology Cancers Healthcare Onco Pathophysiology Toxics Biomolecules IJMS

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17 pages, 3718 KiB  

Open AccessArticle

Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages

by Riccardo Leinardi, Jasmine Rita Petriglieri, Amandine Pochet, Yousof Yakoub, Marie Lelong, Alain Lescoat, Francesco Turci, Valérie Lecureur and François Huaux

Int. J. Mol. Sci. 2023, 24(20), 15145; https://doi.org/10.3390/ijms242015145 - 13 Oct 2023

Cited by 5 | Viewed by 2322

Abstract

While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short [...] Read more.

While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short (SFA) or long (LFA) fibers of amosite asbestos different in size and surface chemistry, we observed that SFA internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses to non-internalizable LFA were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis. SFA effects exclusively resulted from Toll-like receptor 4 (TLR4), a pattern-recognition receptor (PRR) recognized for its ability to sense particles, while the response to LFA was elicited by a multifactorial ignition system involving the macrophage receptor with collagenous structure (SR-A6 or MARCO), reactive oxygen species (ROS) cascade, and TLR4. Our findings indicate that asbestos fiber size and surface features play major roles in modulating ICD and inflammatory pathways. They also suggest that SFA are biologically reactive in vitro and, therefore, their inflammatory and toxic effects in vivo should not be underestimated. Full article

(This article belongs to the Topic Molecular Mechanisms of the Toxicity and Carcinogenicity of Particulates)

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18 pages, 6615 KiB  

Open AccessArticle

Top-Down Preparation of Nanoquartz for Toxicological Investigations

by Chiara Bellomo, Cristina Pavan, Gianluca Fiore, Guillermo Escolano-Casado, Lorenzo Mino and Francesco Turci

Int. J. Mol. Sci. 2022, 23(23), 15425; https://doi.org/10.3390/ijms232315425 - 6 Dec 2022

Cited by 4 | Viewed by 2225

Abstract

Occupational exposure to quartz dust is associated with fatal diseases. Quartz dusts generated by mechanical fracturing are characterized by a broad range of micrometric to nanometric particles. The contribution of this nanometric fraction to the overall toxicity of quartz is still largely unexplored, [...] Read more.

Occupational exposure to quartz dust is associated with fatal diseases. Quartz dusts generated by mechanical fracturing are characterized by a broad range of micrometric to nanometric particles. The contribution of this nanometric fraction to the overall toxicity of quartz is still largely unexplored, primarily because of the strong electrostatic adhesion forces that prevent isolation of the nanofraction. Furthermore, fractured silica dust exhibits special surface features, namely nearly free silanols (NFS), which impart a membranolytic activity to quartz. Nanoquartz can be synthetized via bottom-up methods, but the surface chemistry of such crystals strongly differs from that of nanoparticles resulting from fracturing. Here, we report a top-down milling procedure to obtain a nanometric quartz that shares the key surface properties relevant to toxicity with fractured quartz. The ball milling was optimized by coupling the dry and wet milling steps, using water as a dispersing agent, and varying the milling times and rotational speeds. Nanoquartz with a strong tendency to form submicrometric agglomerates was obtained. The deagglomeration with surfactants or simulated body fluids was negligible. Partial lattice amorphization and a bimodal crystallite domain size were observed. A moderate membranolytic activity, which correlated with the number of NFS, signaled coherence with the previous toxicological data. A membranolytic nanoquartz for toxicological investigations was obtained. Full article

(This article belongs to the Topic Molecular Mechanisms of the Toxicity and Carcinogenicity of Particulates)

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16 pages, 2885 KiB  

Open AccessArticle

Hematotoxic Effect of Respiratory Exposure to PHMG-p and Its Integrated Genetic Analysis

by Hwa Jung Sung, Sang Hoon Jeong, Ja Young Kang, Cherry Kim, Yoon Jeong Nam, Jae Young Kim, Jin Young Choi, Hye Jin Lee, Yu Seon Lee, Eun Yeob Kim, Yong Wook Baek, Hong Lee and Ju Han Lee

Toxics 2022, 10(11), 694; https://doi.org/10.3390/toxics10110694 - 16 Nov 2022

Cited by 2 | Viewed by 2741

Abstract

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in [...] Read more.

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to ‘hematological system development and function’ and ‘hematological disease.’ Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract. Full article

(This article belongs to the Topic Molecular Mechanisms of the Toxicity and Carcinogenicity of Particulates)

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