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Toxicogenomics and Molecular Markers in Pollution

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 April 2022) | Viewed by 28766

Special Issue Editor

Laboratório de Farmacologia Molecular (Instituto de Ciências Biológicas), Universidade Federal do Pará, Belém 66075-110, Brazil

Special Issue Information

Dear Colleagues,

Pollutants, such as pesticides, heavy metals, microplastics, and carbon monoxide among others, are increasingly present in our daily lives, affecting our environment and our bodies. This Special Issue aims to show in a comprehensive way the molecular influence of these pollutants, highlighting original findings that help prevent, reduce, or reverse their effects.

This Special Issue includes, but is not limited to, the following topics:

  • genetic susceptibility and/or epigenetics of pollutants
  • molecular markers of pollution in the environment and/or the human populations
  • evidence-based toxicogenomics and/or molecular biology of pollution (systematic reviews and/or meta-analysis)
  • in vitro and/or in vivo models of pollution
  • prevention and/or remediation strategies against pollution
  • molecular modulation of the effects of pollutants

I encourage all those interested in this Special Issue to submit original research and review articles in the field, with a focus on (but not limited to) its molecular aspects.

Prof. Dr. Maria Elena Crespo-Lopez
Guest Editor

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

  • pollutant
  • contamination
  • pollution
  • toxicology
  • toxicogenomics
  • epigenetics
  • molecular markers
  • epidemiology
  • exposure
  • intoxication
  • genetic susceptibility

Published Papers (10 papers)

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Editorial

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4 pages, 206 KiB  
Editorial
Toxicogenomics and Molecular Markers in Pollution
by Maria Elena Crespo-Lopez
Int. J. Mol. Sci. 2022, 23(15), 8280; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158280 - 27 Jul 2022
Viewed by 1014
Abstract
Pollution is defined as the presence in or introduction of a substance into the environment that has harmful or poisonous effects [...] Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)

Research

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19 pages, 3334 KiB  
Article
Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG
by Katrin Kreuzer, Heike Sprenger and Albert Braeuning
Int. J. Mol. Sci. 2022, 23(7), 3420; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073420 - 22 Mar 2022
Cited by 1 | Viewed by 1951
Abstract
Transcript signatures are a promising approach to identify and classify genotoxic and non-genotoxic compounds and are of interest as biomarkers or for future regulatory application. Not much data, however, is yet available about the concordance of transcriptional responses in different cell types or [...] Read more.
Transcript signatures are a promising approach to identify and classify genotoxic and non-genotoxic compounds and are of interest as biomarkers or for future regulatory application. Not much data, however, is yet available about the concordance of transcriptional responses in different cell types or tissues. Here, we analyzed transcriptomic responses to selected genotoxic food contaminants in the human p53-competent lymphoblastoid cell line TK6 using RNA sequencing. Responses to treatment with five genotoxins, as well as with four non-genotoxic liver toxicants, were compared with previously published gene expression data from the human liver cell model HepaRG. A significant overlap of the transcriptomic changes upon genotoxic stress was detectable in TK6 cells, whereas the comparison with the HepaRG model revealed considerable differences, which was confirmed by bioinformatic data mining for cellular upstream regulators or pathways. Taken together, the study presents a transcriptomic signature for genotoxin exposure in the human TK6 blood cell model. The data demonstrate that responses in different cell models have considerable variations. Detection of a transcriptomic genotoxin signature in blood cells indicates that gene expression analyses of blood samples might be a valuable approach to also estimate responses to toxic exposure in target organs such as the liver. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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18 pages, 20913 KiB  
Article
Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution
by Katerina Honkova, Andrea Rossnerova, Irena Chvojkova, Alena Milcova, Hasmik Margaryan, Anna Pastorkova, Antonin Ambroz, Pavel Rossner, Jr., Vitezslav Jirik, Jiri Rubes, Radim J. Sram and Jan Topinka
Int. J. Mol. Sci. 2022, 23(3), 1666; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031666 - 31 Jan 2022
Cited by 14 | Viewed by 3051
Abstract
DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city [...] Read more.
DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = −1.92, p = 8.30 × 10−4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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19 pages, 2331 KiB  
Article
Developmental Exposure to Low Concentrations of Methylmercury Causes Increase in Anxiety-Related Behaviour and Locomotor Impairments in Zebrafish
by Lilah Glazer and Caroline H. Brennan
Int. J. Mol. Sci. 2021, 22(20), 10961; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010961 - 11 Oct 2021
Cited by 4 | Viewed by 1600
Abstract
Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and [...] Read more.
Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and long-term effects of developmental exposure to low doses of MeHg on anxiety-related behaviours in zebrafish, and to test the involvement of neurological pathways related to stress-response. Zebrafish embryos were exposed to sub-acute doses of MeHg (0, 5, 10, 15, 30 nM) throughout embryo-development, and tested for anxiety-related behaviours and locomotor activity at larval (light/dark locomotor activity) and adult (novel tank and tap assays) life-stages. Exposure to all doses of MeHg caused increased anxiety-related responses; heightened response to the transition from light to dark in larvae, and a stronger dive response in adults. In addition, impairment in locomotor activity was observed in the higher doses in both larvae and adults. Finally, the expressions of several neural stress-response genes from the HPI-axis and dopaminergic system were found to be disrupted in both life-stages. Our results provide important insights into dose-dependent differences in exposure outcomes, the development of delayed effects over the life-time of exposed individuals and the potential mechanisms underlying these effects. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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16 pages, 1590 KiB  
Article
Contributing to Understand the Crosstalk between Brain and Periphery in Methylmercury Intoxication: Neurotoxicity and Extracellular Vesicles
by Gabriela de Paula Arrifano, Marcus Augusto-Oliveira, Megan Sealey-Bright, Jaezah Zainal, Luciana Imbiriba, Luanna Melo Pereira Fernandes, Cristiane Socorro Ferraz Maia, Daniel Anthony and Maria Elena Crespo-Lopez
Int. J. Mol. Sci. 2021, 22(19), 10855; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910855 - 07 Oct 2021
Cited by 5 | Viewed by 1858
Abstract
Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes [...] Read more.
Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes associated with behavioral alterations in MeHg acute exposure and the possible changes in extracellular vesicles (EVs) number and S100β content. Adults male Wistar rats were orally treated with 5 mg/kg for four days. Behavioral performance, molecular and histological changes in the cerebellum, and plasma EVs were assessed. MeHg-intoxicated animals performed significantly worse in behavioral tests. MeHg increased the number of GFAP+ cells and GFAP and S100β mRNA expression in the cerebellum but no change in NeuN+ or IBA-1+ cells number was detected. The number of exosomes isolated from plasma were decreased by the metal. S100B mRNA was detected in circulating plasma EVs cargo in MeHg exposure. Though preliminary, our results suggest astrocytic reactivity is displaying a protective role once there was no neuronal death. Interestingly, the reduction in exosomes number could be a new mechanism associated with MeHg-induced neurotoxicity and plasma EVs could represent a source of future biomarkers in MeHg intoxication. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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18 pages, 2649 KiB  
Article
Dependence of Graphene Oxide (GO) Toxicity on Oxidation Level, Elemental Composition, and Size
by Tao Jiang, Carlo Alberto Amadei, Yishan Lin, Na Gou, Sheikh Mokhlesur Rahman, Jiaqi Lan, Chad D. Vecitis and April Z. Gu
Int. J. Mol. Sci. 2021, 22(19), 10578; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910578 - 30 Sep 2021
Cited by 10 | Viewed by 2144
Abstract
The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. [...] Read more.
The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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18 pages, 16003 KiB  
Article
Generation of Knockout and Transgenic Zebrafish to Characterize Abcc4 Functions in Detoxification and Efflux of Lead
by Xing Lu, Yong Long, Xixi Li, Lang Zhang, Qing Li, Hua Wen, Shan Zhong and Zongbin Cui
Int. J. Mol. Sci. 2021, 22(4), 2054; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042054 - 19 Feb 2021
Cited by 8 | Viewed by 2572
Abstract
Lead (Pb) is one of the major heavy metals that are toxic to vertebrates and usually considered as environmental pollutants. ABCC4/MRP4 is an organic anion transporter that mediates cellular efflux of a wide range of exogenous and endogenous compounds such as cyclic nucleotides [...] Read more.
Lead (Pb) is one of the major heavy metals that are toxic to vertebrates and usually considered as environmental pollutants. ABCC4/MRP4 is an organic anion transporter that mediates cellular efflux of a wide range of exogenous and endogenous compounds such as cyclic nucleotides and anti-cancer drugs; however, it remains unclear whether ABCC4 and its orthologs function in the detoxification and excretion of toxic lead. In this study, we found that the transcriptional and translational expression of zebrafish abcc4 was significantly induced under lead exposure in developing zebrafish embryos and adult tissues. Overexpression of zebrafish Abcc4 markedly decreased the cytotoxicity and accumulation of lead in pig renal proximal tubule cell line (LLC-PK1 cells). To further understand the functions of zebrafish Abcc4 in lead detoxification, the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system was used to create an abcc4−/− mutant zebrafish line. In comparison with the wild-type (WT) zebrafish, the abcc4−/− mutants showed a higher death rate and lead accumulation upon exposure to lead. Furthermore, a stable abcc4-transgenic zebrafish line was successfully generated, which exerted stronger ability to detoxify and excrete lead than WT zebrafish. These findings indicate that zebrafish Abcc4 plays a crucial role in lead detoxification and cellular efflux and could be used as a potential biomarker to monitor lead contamination in a water environment. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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Review

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26 pages, 28093 KiB  
Review
Impact of Air Pollution in Airway Diseases: Role of the Epithelial Cells (Cell Models and Biomarkers)
by Giusy Daniela Albano, Angela Marina Montalbano, Rosalia Gagliardo, Giulia Anzalone and Mirella Profita
Int. J. Mol. Sci. 2022, 23(5), 2799; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052799 - 03 Mar 2022
Cited by 11 | Viewed by 3778
Abstract
Biomedical research is multidisciplinary and often uses integrated approaches performing different experimental models with complementary functions. This approach is important to understand the pathogenetic mechanisms concerning the effects of environmental pollution on human health. The biological activity of the substances is investigated at [...] Read more.
Biomedical research is multidisciplinary and often uses integrated approaches performing different experimental models with complementary functions. This approach is important to understand the pathogenetic mechanisms concerning the effects of environmental pollution on human health. The biological activity of the substances is investigated at least to three levels using molecular, cellular, and human tissue models. Each of these is able to give specific answers to experimental problems. A scientific approach, using biological methods (wet lab), cell cultures (cell lines or primary), isolated organs (three-dimensional cell cultures of primary epithelial cells), and animal organisms, including the human body, aimed to understand the effects of air pollution on the onset of diseases of the respiratory system. Biological methods are divided into three complementary models: in vitro, ex vivo, and in vivo. In vitro experiments do not require the use of whole organisms (in vivo study), while ex vivo experiments use isolated organs or parts of organs. The concept of complementarity and the informatic support are useful tools to organize, analyze, and interpret experimental data, with the aim of discussing scientific notions with objectivity and rationality in biology and medicine. In this scenario, the integrated and complementary use of different experimental models is important to obtain useful and global information that allows us to identify the effect of inhaled pollutants on the incidence of respiratory diseases in the exposed population. In this review, we focused our attention on the impact of air pollution in airway diseases with a rapid and descriptive analysis on the role of epithelium and on the experimental cell models useful to study the effect of toxicants on epithelial cells. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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15 pages, 2664 KiB  
Review
Methylmercury plus Ethanol Exposure: How Much Does This Combination Affect Emotionality?
by Diandra Araújo Luz, Sabrina de Carvalho Cartágenes, Cinthia Cristina Sousa de Menezes da Silveira, Bruno Gonçalves Pinheiro, Kissila Márvia Matias Machado Ferraro, Luanna de Melo Pereira Fernandes, Enéas Andrade Fontes-Júnior and Cristiane do Socorro Ferraz Maia
Int. J. Mol. Sci. 2021, 22(23), 13131; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313131 - 04 Dec 2021
Cited by 2 | Viewed by 2239
Abstract
Mercury is a heavy metal found in organic and inorganic forms that represents an important toxicant with impact on human health. Mercury can be released in the environment by natural phenoms (i.e., volcanic eruptions), industrial products, waste, or anthropogenic actions (i.e., mining activity). [...] Read more.
Mercury is a heavy metal found in organic and inorganic forms that represents an important toxicant with impact on human health. Mercury can be released in the environment by natural phenoms (i.e., volcanic eruptions), industrial products, waste, or anthropogenic actions (i.e., mining activity). Evidence has pointed to mercury exposure inducing neurological damages related to emotional disturbance, such as anxiety, depression, and insomnia. The mechanisms that underlie these emotional disorders remain poorly understood, although an important role of glutamatergic pathways, alterations in HPA axis, and disturbance in activity of monoamines have been suggested. Ethanol (EtOH) is a psychoactive substance consumed worldwide that induces emotional alterations that have been strongly investigated, and shares common pathophysiological mechanisms with mercury. Concomitant mercury and EtOH intoxication occur in several regions of the world, specially by communities that consume seafood and fish as the principal product of nutrition (i.e., Amazon region). Such affront appears to be more deleterious in critical periods of life, such as the prenatal and adolescence period. Thus, this review aimed to discuss the cellular and behavioral changes displayed by the mercury plus EtOH exposure during adolescence, focused on emotional disorders, to answer the question of whether mercury plus EtOH exposure intensifies depression, anxiety, and insomnia observed by the toxicants in isolation. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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25 pages, 1102 KiB  
Review
Cellular and Molecular Mechanisms Mediating Methylmercury Neurotoxicity and Neuroinflammation
by João P. Novo, Beatriz Martins, Ramon S. Raposo, Frederico C. Pereira, Reinaldo B. Oriá, João O. Malva and Carlos Fontes-Ribeiro
Int. J. Mol. Sci. 2021, 22(6), 3101; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063101 - 18 Mar 2021
Cited by 34 | Viewed by 7525
Abstract
Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also [...] Read more.
Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies. Full article
(This article belongs to the Special Issue Toxicogenomics and Molecular Markers in Pollution)
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