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Toxics
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Biomarkers of Environmental Toxicants
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Biomarkers of Environmental Toxicants

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome".

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 105370

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Kun LU

E-Mail Website
Guest Editor
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
Interests: biomarker development; DNA adducts; metabolomics; proteomics; microbiome
Prof. Dr. Robert J. Turesky

E-Mail Website
Guest Editor
Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
Interests: metabolism; biomarkers; mass spectrometry; environmental toxicants

Special Issue Information

Dear Colleagues,

Biomarkers are commonly used to evaluate exposure and biological effects of environmental toxicants. Characterization and development of sensitive and robust biomarkers have remained active over the last few decades to study the toxicity of environmental toxicants and human disease. There is a are clear need to further discover, validate and apply biomarkers in toxicological research, population-based studies, risk assessment and beyond. This Special Issue on “Biomarkers of Environmental Toxicants” will aim at highlighting the latest advances in biomarker-related research in a timely manner. Authors are invited to submit original research papers, reviews, and short communications.

Topics may include, but are not limited to, the following:

  1. Discovery or validation of new biomarkers of exposure and effects of environmental toxicants. These biomarkers could be DNA adducts, protein adducts, metabolites, enzymes, or any relevant biological molecules or indicators.
  2. Omics profiling, such as metabolomics and proteomics, to study the effects of environmental toxicants with the goal of developing potential biomarkers.
  3. Novel methods or assays for biomarker development.
  4. Development or analysis of compound- or organ-specific biomarkers.
  5. Development of microbiome as potential biomarkers.
  6. Characterization or measurement of biomarkers in human populations or selected cohorts.

Prof. Dr. Robert J. Turesky
Prof. Dr. Kun LU
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. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • biomarker
  • environmental toxicants
  • metabolomics
  • proteomics
  • method development
  • microbiome
  • population
  • risk assessment

Published Papers (15 papers)

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Editorial

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4 pages, 188 KiB  
Editorial
Biomarkers of Environmental Toxicants: Exposure and Biological Effects
by Robert J. Turesky and Kun Lu
Toxics 2020, 8(2), 37; https://doi.org/10.3390/toxics8020037 - 22 May 2020
Cited by 8 | Viewed by 3096
Abstract
Biomarkers of environmental toxicants are measures of exposures and effects, some of which can serve to assess disease risk and interindividual susceptibilities [...] Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)

Research

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13 pages, 2445 KiB  
Article
Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk
by Jenny Aasa, Efstathios Vryonidis, Lilianne Abramsson-Zetterberg and Margareta Törnqvist
Toxics 2019, 7(1), 7; https://doi.org/10.3390/toxics7010007 - 01 Feb 2019
Cited by 14 | Viewed by 4564
Abstract
The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 [...] Read more.
The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 μg/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/105) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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8 pages, 243 KiB  
Article
Biomonitoring of Urinary Benzene Metabolite SPMA in the General Population in Central Italy
by Giovanna Tranfo, Daniela Pigini, Enrico Paci, Lisa Bauleo, Francesco Forastiere and Carla Ancona
Toxics 2018, 6(3), 37; https://doi.org/10.3390/toxics6030037 - 11 Jul 2018
Cited by 18 | Viewed by 4109
Abstract
Background: Benzene is an important component of cigarette smoke and car exhaust. Products containing benzene in concentrations greater than 0.1% are prohibited in Europe, but 1% of benzene is still allowed in gasoline. The purpose of the study was to assess the levels [...] Read more.
Background: Benzene is an important component of cigarette smoke and car exhaust. Products containing benzene in concentrations greater than 0.1% are prohibited in Europe, but 1% of benzene is still allowed in gasoline. The purpose of the study was to assess the levels of urine benzene biomarkers in a sample of the general population not occupationally exposed to benzene, resident in the period 2013–2014 in Central Italy, compared to other groups. Methods: The urinary levels of the benzene metabolites S-phenyl-mercapturic acid (SPMA) and cotinine (nicotine metabolite) were determined by means of HPLC with mass spectrometric detection in 1076 subjects. Results: The median SPMA value in smokers was 1.132 µg/g of creatinine while in non-smokers it was 0.097 µg/g of creatinine, and the 95th percentile results were seven times higher. Conclusion: The main source of benzene exposure in the studied population was active smoking, however, non-smokers were also exposed to airborne benzene concentrations. The concentration ranges found in this study can be used as a background reference for occupational exposure assessment to benzene by means of SPMA biomonitoring. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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15 pages, 1840 KiB  
Article
Determinants of Hair Manganese, Lead, Cadmium and Arsenic Levels in Environmentally Exposed Children
by Thomas Jursa, Cheryl R. Stein and Donald R. Smith
Toxics 2018, 6(2), 19; https://doi.org/10.3390/toxics6020019 - 22 Mar 2018
Cited by 29 | Viewed by 5283
Abstract
Biomarkers of environmental metal exposure in children are important for elucidating exposure and health risk. While exposure biomarkers for As, Cd, and Pb are relatively well defined, there are not yet well-validated biomarkers of Mn exposure. Here, we measured hair Mn, Pb, Cd, [...] Read more.
Biomarkers of environmental metal exposure in children are important for elucidating exposure and health risk. While exposure biomarkers for As, Cd, and Pb are relatively well defined, there are not yet well-validated biomarkers of Mn exposure. Here, we measured hair Mn, Pb, Cd, and As levels in children from the Mid-Ohio Valley to determine within and between-subject predictors of hair metal levels. Occipital scalp hair was collected in 2009–2010 from 222 children aged 6–12 years (169 female, 53 male) participating in a study of chemical exposure and neurodevelopment in an industrial region of the Mid-Ohio Valley. Hair samples from females were divided into three two centimeter segments, while males provided a single segment. Hair was cleaned and processed in a trace metal clean laboratory, and analyzed for As, Cd, Mn, and Pb by magnetic sector inductively coupled plasma mass spectrometry. Hair Mn and Pb levels were comparable (median 0.11 and 0.15 µg/g, respectively) and were ~10-fold higher than hair Cd and As levels (0.007 and 0.018 µg/g, respectively). Hair metal levels were higher in males compared to females, and varied by ~100–1000-fold between all subjects, and substantially less (<40–70%) between segments within female subjects. Hair Mn, Pb, and Cd, but not As levels systematically increased by ~40–70% from the proximal to distal hair segments of females. There was a significant effect of season of hair sample collection on hair Mn, Pb, and Cd, but not As levels. Finally, hair metal levels reported here are ~2 to >10-fold lower than levels reported in other studies in children, most likely because of more rigorous hair cleaning methodology used in the present study, leading to lower levels of unresolved exogenous metal contamination of hair. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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Review

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18 pages, 1160 KiB  
Review
Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases
by Pengcheng Tu, Liang Chi, Wanda Bodnar, Zhenfa Zhang, Bei Gao, Xiaoming Bian, Jill Stewart, Rebecca Fry and Kun Lu
Toxics 2020, 8(1), 19; https://doi.org/10.3390/toxics8010019 - 12 Mar 2020
Cited by 62 | Viewed by 12315
Abstract
The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an [...] Read more.
The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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19 pages, 692 KiB  
Review
Towards Mass Spectrometry-Based Chemical Exposome: Current Approaches, Challenges, and Future Directions
by Jingchuan Xue, Yunjia Lai, Chih-Wei Liu and Hongyu Ru
Toxics 2019, 7(3), 41; https://doi.org/10.3390/toxics7030041 - 18 Aug 2019
Cited by 27 | Viewed by 5610
Abstract
The proposal of the “exposome” concept represents a shift of the research paradigm in studying exposure-disease relationships from an isolated and partial way to a systematic and agnostic approach. Nevertheless, exposome implementation is facing a variety of challenges including measurement techniques and data [...] Read more.
The proposal of the “exposome” concept represents a shift of the research paradigm in studying exposure-disease relationships from an isolated and partial way to a systematic and agnostic approach. Nevertheless, exposome implementation is facing a variety of challenges including measurement techniques and data analysis. Here we focus on the chemical exposome, which refers to the mixtures of chemical pollutants people are exposed to from embryo onwards. We review the current chemical exposome measurement approaches with a focus on those based on the mass spectrometry. We further explore the strategies in implementing the concept of chemical exposome and discuss the available chemical exposome studies. Early progresses in the chemical exposome research are outlined, and major challenges are highlighted. In conclusion, efforts towards chemical exposome have only uncovered the tip of the iceberg, and further advancement in measurement techniques, computational tools, high-throughput data analysis, and standardization may allow more exciting discoveries concerning the role of exposome in human health and disease. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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18 pages, 3180 KiB  
Review
Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner
by Ke Bian, James C. Delaney, Xianhao Zhou and Deyu Li
Toxics 2019, 7(2), 36; https://doi.org/10.3390/toxics7020036 - 25 Jun 2019
Cited by 3 | Viewed by 3641
Abstract
As described elsewhere in this Special Issue on biomarkers, much progress has been made in the detection of modified DNA within organisms at endogenous and exogenous levels of exposure to chemical species, including putative carcinogens and chemotherapeutic agents. Advances in the detection of [...] Read more.
As described elsewhere in this Special Issue on biomarkers, much progress has been made in the detection of modified DNA within organisms at endogenous and exogenous levels of exposure to chemical species, including putative carcinogens and chemotherapeutic agents. Advances in the detection of damaged or unnatural bases have been able to provide correlations to support or refute hypotheses between the level of exposure to oxidative, alkylative, and other stresses, and the resulting DNA damage (lesion formation). However, such stresses can form a plethora of modified nucleobases, and it is therefore difficult to determine the individual contribution of a particular modification to alter a cell’s genetic fate, as measured in the form of toxicity by stalled replication past the damage, by subsequent mutation, and by lesion repair. Chemical incorporation of a modification at a specific site within a vector (site-specific mutagenesis) has been a useful tool to deconvolute what types of damage quantified in biologically relevant systems may lead to toxicity and/or mutagenicity, thereby allowing researchers to focus on the most relevant biomarkers that may impact human health. Here, we will review a sampling of the DNA modifications that have been studied by shuttle vector techniques. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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35 pages, 3057 KiB  
Review
Bioanalytical and Mass Spectrometric Methods for Aldehyde Profiling in Biological Fluids
by Romel P. Dator, Morwena J. Solivio, Peter W. Villalta and Silvia Balbo
Toxics 2019, 7(2), 32; https://doi.org/10.3390/toxics7020032 - 04 Jun 2019
Cited by 31 | Viewed by 8424
Abstract
Human exposure to aldehydes is implicated in multiple diseases including diabetes, cardiovascular diseases, neurodegenerative disorders (i.e., Alzheimer’s and Parkinson’s Diseases), and cancer. Because these compounds are strong electrophiles, they can react with nucleophilic sites in DNA and proteins to form reversible and irreversible [...] Read more.
Human exposure to aldehydes is implicated in multiple diseases including diabetes, cardiovascular diseases, neurodegenerative disorders (i.e., Alzheimer’s and Parkinson’s Diseases), and cancer. Because these compounds are strong electrophiles, they can react with nucleophilic sites in DNA and proteins to form reversible and irreversible modifications. These modifications, if not eliminated or repaired, can lead to alteration in cellular homeostasis, cell death and ultimately contribute to disease pathogenesis. This review provides an overview of the current knowledge of the methods and applications of aldehyde exposure measurements, with a particular focus on bioanalytical and mass spectrometric techniques, including recent advances in mass spectrometry (MS)-based profiling methods for identifying potential biomarkers of aldehyde exposure. We discuss the various derivatization reagents used to capture small polar aldehydes and methods to quantify these compounds in biological matrices. In addition, we present emerging mass spectrometry-based methods, which use high-resolution accurate mass (HR/AM) analysis for characterizing carbonyl compounds and their potential applications in molecular epidemiology studies. With the availability of diverse bioanalytical methods presented here including simple and rapid techniques allowing remote monitoring of aldehydes, real-time imaging of aldehydic load in cells, advances in MS instrumentation, high performance chromatographic separation, and improved bioinformatics tools, the data acquired enable increased sensitivity for identifying specific aldehydes and new biomarkers of aldehyde exposure. Finally, the combination of these techniques with exciting new methods for single cell analysis provides the potential for detection and profiling of aldehydes at a cellular level, opening up the opportunity to minutely dissect their roles and biological consequences in cellular metabolism and diseases pathogenesis. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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17 pages, 805 KiB  
Review
Protein Adductomics: Analytical Developments and Applications in Human Biomonitoring
by George W. Preston and David H. Phillips
Toxics 2019, 7(2), 29; https://doi.org/10.3390/toxics7020029 - 25 May 2019
Cited by 13 | Viewed by 4999
Abstract
Proteins contain many sites that are subject to modification by electrophiles. Detection and characterisation of these modifications can give insights into environmental agents and endogenous processes that may be contributing factors to chronic human diseases. An untargeted approach, utilising mass spectrometry to detect [...] Read more.
Proteins contain many sites that are subject to modification by electrophiles. Detection and characterisation of these modifications can give insights into environmental agents and endogenous processes that may be contributing factors to chronic human diseases. An untargeted approach, utilising mass spectrometry to detect modified amino acids or peptides, has been applied to blood proteins haemoglobin and albumin, focusing in particular on the N-terminal valine residue of haemoglobin and the cysteine-34 residue in albumin. Technical developments to firstly detect simultaneously multiple adducts at these sites and then subsequently to identify them are reviewed here. Recent studies in which the methods have been applied to biomonitoring human exposure to environmental toxicants are described. With advances in sensitivity, high-throughput handling of samples and robust quality control, these methods have considerable potential for identifying causes of human chronic disease and of identifying individuals at risk. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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22 pages, 4333 KiB  
Review
Radiocarbon Tracers in Toxicology and Medicine: Recent Advances in Technology and Science
by Michael A. Malfatti, Bruce A. Buchholz, Heather A. Enright, Benjamin J. Stewart, Ted J. Ognibene, A. Daniel McCartt, Gabriela G. Loots, Maike Zimmermann, Tiffany M. Scharadin, George D. Cimino, Brian A. Jonas, Chong-Xian Pan, Graham Bench, Paul T. Henderson and Kenneth W. Turteltaub
Toxics 2019, 7(2), 27; https://doi.org/10.3390/toxics7020027 - 09 May 2019
Cited by 9 | Viewed by 5278
Abstract
This review summarizes recent developments in radiocarbon tracer technology and applications. Technologies covered include accelerator mass spectrometry (AMS), including conversion of samples to graphite, and rapid combustion to carbon dioxide to enable direct liquid sample analysis, coupling to HPLC for real-time AMS analysis, [...] Read more.
This review summarizes recent developments in radiocarbon tracer technology and applications. Technologies covered include accelerator mass spectrometry (AMS), including conversion of samples to graphite, and rapid combustion to carbon dioxide to enable direct liquid sample analysis, coupling to HPLC for real-time AMS analysis, and combined molecular mass spectrometry and AMS for analyte identification and quantitation. Laser-based alternatives, such as cavity ring down spectrometry, are emerging to enable lower cost, higher throughput measurements of biological samples. Applications covered include radiocarbon dating, use of environmental atomic bomb pulse radiocarbon content for cell and protein age determination and turnover studies, and carbon source identification. Low dose toxicology applications reviewed include studies of naphthalene-DNA adduct formation, benzo[a]pyrene pharmacokinetics in humans, and triclocarban exposure and risk assessment. Cancer-related studies covered include the use of radiocarbon-labeled cells for better defining mechanisms of metastasis and the use of drug-DNA adducts as predictive biomarkers of response to chemotherapy. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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28 pages, 2752 KiB  
Review
A Review of Biomonitoring of Phthalate Exposures
by Yu Wang, Hongkai Zhu and Kurunthachalam Kannan
Toxics 2019, 7(2), 21; https://doi.org/10.3390/toxics7020021 - 05 Apr 2019
Cited by 414 | Viewed by 20638
Abstract
Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been [...] Read more.
Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been recognized as substances of high concern. Human exposure to phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites. Metabolites of diethyl phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of phthalates and exposure doses to assess health risks from phthalate exposures in populations across the globe. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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18 pages, 4745 KiB  
Review
The Versatile Roles of the tRNA Epitranscriptome during Cellular Responses to Toxic Exposures and Environmental Stress
by Sabrina M. Huber, Andrea Leonardi, Peter C. Dedon and Thomas J. Begley
Toxics 2019, 7(1), 17; https://doi.org/10.3390/toxics7010017 - 25 Mar 2019
Cited by 42 | Viewed by 5751
Abstract
Living organisms respond to environmental changes and xenobiotic exposures by regulating gene expression. While heat shock, unfolded protein, and DNA damage stress responses are well-studied at the levels of the transcriptome and proteome, tRNA-mediated mechanisms are only recently emerging as important modulators of [...] Read more.
Living organisms respond to environmental changes and xenobiotic exposures by regulating gene expression. While heat shock, unfolded protein, and DNA damage stress responses are well-studied at the levels of the transcriptome and proteome, tRNA-mediated mechanisms are only recently emerging as important modulators of cellular stress responses. Regulation of the stress response by tRNA shows a high functional diversity, ranging from the control of tRNA maturation and translation initiation, to translational enhancement through modification-mediated codon-biased translation of mRNAs encoding stress response proteins, and translational repression by stress-induced tRNA fragments. tRNAs need to be heavily modified post-transcriptionally for full activity, and it is becoming increasingly clear that many aspects of tRNA metabolism and function are regulated through the dynamic introduction and removal of modifications. This review will discuss the many ways that nucleoside modifications confer high functional diversity to tRNAs, with a focus on tRNA modification-mediated regulation of the eukaryotic response to environmental stress and toxicant exposures. Additionally, the potential applications of tRNA modification biology in the development of early biomarkers of pathology will be highlighted. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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28 pages, 2619 KiB  
Review
Recent Studies on DNA Adducts Resulting from Human Exposure to Tobacco Smoke
by Bin Ma, Irina Stepanov and Stephen S. Hecht
Toxics 2019, 7(1), 16; https://doi.org/10.3390/toxics7010016 - 19 Mar 2019
Cited by 52 | Viewed by 7492
Abstract
DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. We have summarized research conducted since 2012 on DNA adduct formation in smokers. A variety of [...] Read more.
DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. We have summarized research conducted since 2012 on DNA adduct formation in smokers. A variety of DNA adducts derived from various classes of carcinogens, including aromatic amines, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, alkylating agents, aldehydes, volatile carcinogens, as well as oxidative damage have been reported. The results are discussed with particular attention to the analytical methods used in those studies. Mass spectrometry-based methods that have higher selectivity and specificity compared to 32P-postlabeling or immunochemical approaches are preferred. Multiple DNA adducts specific to tobacco constituents have also been characterized for the first time in vitro or detected in vivo since 2012, and descriptions of those adducts are included. We also discuss common issues related to measuring DNA adducts in humans, including the development and validation of analytical methods and prevention of artifact formation. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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20 pages, 3719 KiB  
Review
Formalin-Fixed Paraffin-Embedded Tissues—An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry
by Byeong Hwa Yun, Jingshu Guo and Robert J. Turesky
Toxics 2018, 6(2), 30; https://doi.org/10.3390/toxics6020030 - 01 Jun 2018
Cited by 7 | Viewed by 6886
Abstract
The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and [...] Read more.
The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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Other

14 pages, 5671 KiB  
Perspective
Aristolochic Acids: Newly Identified Exposure Pathways of this Class of Environmental and Food-Borne Contaminants and its Potential Link to Chronic Kidney Diseases
by Chi-Kong Chan, Yushuo Liu, Nikola M. Pavlović and Wan Chan
Toxics 2019, 7(1), 14; https://doi.org/10.3390/toxics7010014 - 19 Mar 2019
Cited by 24 | Viewed by 5525
Abstract
Aristolochic acids (AAs) are nitrophenanthrene carboxylic acids naturally produced by Aristolochia plants. These plants were widely used to prepare herbal remedies until AAs were observed to be highly nephrotoxic and carcinogenic to humans. Although the use of AA-containing Aristolochia plants in herbal medicine [...] Read more.
Aristolochic acids (AAs) are nitrophenanthrene carboxylic acids naturally produced by Aristolochia plants. These plants were widely used to prepare herbal remedies until AAs were observed to be highly nephrotoxic and carcinogenic to humans. Although the use of AA-containing Aristolochia plants in herbal medicine is prohibited in countries worldwide, emerging evidence nevertheless has indicated that AAs are the causative agents of Balkan endemic nephropathy (BEN), an environmentally derived disease threatening numerous residents of rural farming villages along the Danube River in countries of the Balkan Peninsula. This perspective updates recent findings on the identification of AAs in food as a result of the root uptake of free AAs released from the decayed seeds of Aristolochia clematitis L., in combination with their presence and fate in the environment. The potential link between AAs and the high prevalence of chronic kidney diseases in China is also discussed. Full article
(This article belongs to the Special Issue Biomarkers of Environmental Toxicants)
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