Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 January 2024) | Viewed by 7075

Share This Special Issue

Special Issue Editors

Dr. Ricard Marcos

E-Mail Website
Guest Editor

Group of Mutagenesis, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Interests: genotoxicity; nanoplastics; biomarkers; DNA damage; nanotoxicology

Dr. Alba Hernandez

E-Mail Website
Guest Editor

Group of Mutagenesis, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
Interests: carcinogenic potential of nanomaterials; NMs exposure; nanotoxicology

Special Issue Information

Dear Colleagues,

Most in vitro studies detect exposure effects using short acute exposures and high (and unrealistic) concentrations. However, there is an alternative approach that represents a more realistic scenario and uses subtoxic concentrations and long-term (weeks) exposures. This Special Issue aims to highlight papers that, under the umbrella of “long-term exposures”, explore the in vitro effects of environmental pollutants in terms of general toxicity or, more specifically, mechanistic aspects such as their carcinogenic and epigenetic effects.

Dr. Ricard Marcos
Dr. Alba Hernandez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

long-term exposure
environmental pollutants
toxicity
carcinogenesis
epigenetic effects
effect biomarkers

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

14 pages, 1603 KiB

Open AccessArticle

Toxicological Profiling and Long-Term Effects of Bare, PEGylated- and Galacto-Oligosaccharide-Functionalized Mesoporous Silica Nanoparticles

by Irene Barguilla, Vicente Candela-Noguera, Patrick Oliver, Balasubramanyam Annangi, Paula Díez, Elena Aznar, Ramón Martínez-Máñez, Ricard Marcos, Alba Hernández and María Dolores Marcos

Int. J. Mol. Sci. 2023, 24(22), 16158; https://doi.org/10.3390/ijms242216158 - 10 Nov 2023

Cited by 2 | Viewed by 856

Abstract

Mesoporous silica nanoparticles (MSNs) are amongst the most used nanoparticles in biomedicine. However, the potentially toxic effects of MSNs have not yet been fully evaluated, being a controversial matter in research. In this study, bare MSNs, PEGylated MSNs (MSNs-PEG), and galacto-oligosaccharide-functionalized MSNs (MSNs-GAL) are synthesized and characterized to assess their genotoxicity and transforming ability on human lung epithelial BEAS-2B cells in short- (48 h) and long-term (8 weeks) exposure scenarios. Initial short-term treatments show a dose-dependent increase in genotoxicity for MSNs-PEG-treated cells but not oxidative DNA damage for MSNs, MSNs-PEG, or for MSNs-GAL. In addition, after 8 weeks of continuous exposure, neither induced genotoxic nor oxidative DNA is observed. Nevertheless, long-term treatment with MSNs-PEG and MSNs-GAL, but not bare MSNs, induces cell transformation features, as evidenced by the cell’s enhanced ability to grow independently of anchorage, to migrate, and to invade. Further, the secretome from cells treated with MSNs and MSNs-GAL, but not MSNs-PEG, shows certain tumor-promoting abilities, increasing the number and size of HeLa cell colonies formed in the indirect soft-agar assay. These results show that MSNs, specifically the functionalized ones, provoke some measurable adverse effects linked to tumorigenesis. These effects are in the order of other nanomaterials, such as carbon nanotubes or cerium dioxide nanoparticles, but they are lower than those provoked by some approved drugs, such as doxorubicin or dexamethasone. Full article

(This article belongs to the Special Issue Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures)

► Show Figures

Figure 1

18 pages, 4071 KiB

Open AccessArticle

Effect of Long-Term Low-Dose Arsenic Exposure on DNA Methylation and Gene Expression in Human Liver Cells

by Sandra Stößer, Tatjana Lumpp, Franziska Fischer, Sarah Gunesch, Paul Schumacher and Andrea Hartwig

Int. J. Mol. Sci. 2023, 24(20), 15238; https://doi.org/10.3390/ijms242015238 - 16 Oct 2023

Cited by 1 | Viewed by 1369

Abstract

Millions of people around the world are exposed to elevated levels of arsenic through food or drinking water. Epidemiological studies have linked chronic arsenic exposure to an increased risk of several cancers, cardiovascular disease, central nervous system neuropathies, and genotoxic as well as immunotoxic effects. In addition to the induction of oxidative stress and inhibition of DNA repair processes, epigenetic effects, including altered DNA methylation patterns resulting in aberrant gene expression, may contribute to carcinogenicity. However, the underlying mechanisms by which chronic micromolar concentrations of arsenite affect the methylation status of DNA are not fully understood. In this study, human HepG2 hepatocarcinoma cells were treated with 0.5–10 μM sodium arsenite for 24 h, 10, or 20 days. During these periods, the effects on global DNA methylation, cell cycle phase distribution, and gene expression were investigated. While no impact on DNA methylation was seen after short-term exposure, global hypomethylation was observed at both long-term exposure periods, with concomitant induction of the DNA methyltransferase genes DNMT1 and DNMT3B, while DNMT3A was slightly down-regulated. Pronounced time- and concentration-dependent effects were also seen in the case of genes involved in DNA damage response and repair, inflammation, oxidative stress response, and metal homeostasis. These results suggest that chronic low-dose arsenite exposure can lead to global hypomethylation. As an underlying mechanism, the consistent down-regulation of DNA methyltransferase genes could be excluded; alternatively, interactions at the protein level could play an important role. Full article

(This article belongs to the Special Issue Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures)

► Show Figures

Figure 1

20 pages, 13665 KiB

Open AccessArticle

Dynamic Alterations to Hepatic MicroRNA-29a in Response to Long-Term High-Fat Diet and EtOH Feeding

by Tiebing Liang, Janaiah Kota, Kent E. Williams, Romil Saxena, Samer Gawrieh, Xiaoling Zhong, Teresa A. Zimmers and Naga Chalasani

Int. J. Mol. Sci. 2023, 24(19), 14564; https://doi.org/10.3390/ijms241914564 - 26 Sep 2023

Viewed by 854

Abstract

MicroRNA-29a (miR-29a) is a well characterized fibro-inflammatory molecule and its aberrant expression is linked to a variety of pathological liver conditions. The long-term effects of a high-fat diet (HFD) in combination with different levels of EtOH consumption on miR-29a expression and liver pathobiology are unknown. Mice at 8 weeks of age were divided into five groups (calorie-matched diet plus water (CMD) as a control group, HFD plus water (HFD) as a liver disease group, HFD plus 2% EtOH (HFD + 2% E), HFD + 10% E, and HFD + 20% E as intervention groups) and fed for 4, 13, 26, or 39 weeks. At each time point, analyses were performed for liver weight/body weight (BW) ratio, AST/ALT ratio, as well as liver histology assessments, which included inflammation, estimated fat deposition, lipid area, and fibrosis. Hepatic miR-29a was measured and correlations with phenotypic traits were determined. Four-week feeding produced no differences between the groups on all collected phenotypic traits or miR-29a expression, while significant effects were observed after 13 weeks, with EtOH concentration-specific induction of miR-29a. A turning point for most of the collected traits was apparent at 26 weeks, and miR-29a was significantly down-regulated with increasing liver injury. Overall, miR-29a up-regulation was associated with a lower liver/BW ratio, fat deposition, inflammation, and fibrosis, suggesting a protective role of miR-29a against liver disease progression. A HFD plus increasing concentrations of EtOH produces progressive adverse effects on the liver, with no evidence of beneficial effects of low-dose EtOH consumption. Moreover, miR-29a up-regulation is associated with less severe liver injury. Full article

(This article belongs to the Special Issue Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures)

► Show Figures

Figure 1

13 pages, 4048 KiB

Open AccessArticle

Chronic Exposure to TDI Induces Cell Migration and Invasion via TGF-β1 Signal Transduction

by Dong-Hee Han, Min Kyoung Shin, Jin Wook Oh, Junha Lee, Jung-Suk Sung and Min Kim

Int. J. Mol. Sci. 2023, 24(7), 6157; https://doi.org/10.3390/ijms24076157 - 24 Mar 2023

Cited by 1 | Viewed by 1387

Abstract

Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, transcriptome analysis results confirmed that TDI increases transforming growth factor-beta 1 (TGF-β1) expression and regulates genes associated with cancerous characteristics in bronchial cells. Our chronically TDI-exposed model exhibited elongated spindle-like morphology, a mesenchymal characteristic. Epithelial-mesenchymal transition (EMT) was evaluated following chronic TDI exposure, and EMT biomarkers increased concentration-dependently. Furthermore, our results indicated diminished cell adhesion molecules and intensified cell migration and invasion. In order to investigate the cellular regulatory mechanisms resulting from chronic TDI exposure, we focused on TGF-β1, a key factor regulated by TDI exposure. As predicted, TGF-β1 was significantly up-regulated and secreted in chronically TDI-exposed cells. In addition, SMAD2/3 was also activated considerably as it is the direct target of TGF-β1 and TGF-β1 receptors. Inhibiting TGF-β1 signaling through blocking of the TGF-β receptor attenuated EMT and cell migration in chronically TDI-exposed cells. Our results corroborate that chronic TDI exposure upregulates TGF-β1 secretion, activates TGF-β1 signal transduction, and leads to EMT and other cancer properties. Full article

(This article belongs to the Special Issue Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures)

► Show Figures

Graphical abstract

Review

Jump to: Research

26 pages, 3667 KiB

Open AccessReview

In Vitro Approaches to Determine the Potential Carcinogenic Risk of Environmental Pollutants

by Irene Barguilla, Veronique Maguer-Satta, Boris Guyot, Susana Pastor, Ricard Marcos and Alba Hernández

Int. J. Mol. Sci. 2023, 24(9), 7851; https://doi.org/10.3390/ijms24097851 - 25 Apr 2023

Cited by 3 | Viewed by 1743

Abstract

One important environmental/health challenge is to determine, in a feasible way, the potential carcinogenic risk associated with environmental agents/exposures. Since a significant proportion of tumors have an environmental origin, detecting the potential carcinogenic risk of environmental agents is mandatory, as regulated by national and international agencies. The challenge mainly implies finding a way of how to overcome the inefficiencies of long-term trials with rodents when thousands of agents/exposures need to be tested. To such an end, the use of in vitro cell transformation assays (CTAs) was proposed, but the existing prevalidated CTAs do not cover the complexity associated with carcinogenesis processes and present serious limitations. To overcome such limitations, we propose to use a battery of assays covering most of the hallmarks of the carcinogenesis process. For the first time, we grouped such assays as early, intermediate, or advanced biomarkers which allow for the identification of the cells in the initiation, promotion or aggressive stages of tumorigenesis. Our proposal, as a novelty, points out that using a battery containing assays from all three groups can identify if a certain agent/exposure can pose a carcinogenic risk; furthermore, it can gather mechanistic insights into the mode of the action of a specific carcinogen. This structured battery could be very useful for any type of in vitro study, containing human cell lines aiming to detect the potential carcinogenic risks of environmental agents/exposures. In fact, here, we include examples in which these approaches were successfully applied. Finally, we provide a series of advantages that, we believe, contribute to the suitability of our proposed approach for the evaluation of exposure-induced carcinogenic effects and for the development of an alternative strategy for conducting an exposure risk assessment. Full article

(This article belongs to the Special Issue Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures)

► Show Figures

Journal Menu

Journal Browser

Long-Term Toxicity, Carcinogenesis, and Epigenetic Effects of Environmental Exposures

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI