2,595 results match your criteria Environmental and Molecular Mutagenesis[Journal]


Differentiation of Aneugens and Clastogens in the In Vitro Micronucleus Test by Kinetochore Scoring Using Automated Image Analysis.

Environ Mol Mutagen 2018 Dec 18. Epub 2018 Dec 18.

Bayer AG, Investigational Toxicology, Berlin, Germany.

The in vitro micronucleus test according to OECD Test Guideline 487 (TG 487) is widely used to investigate the genotoxic potential of drugs. Besides the identification of in vitro genotoxicants, the assay can be complemented with kinetochore staining for the differentiation between clastogens and aneugens. This differentiation constitutes a major contribution to risk assessment as especially aneugens show a threshold response. Read More

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http://dx.doi.org/10.1002/em.22259DOI Listing
December 2018

JAK2 regulates mismatch repair protein-mediated epigenetic alterations in response to oxidative damage.

Environ Mol Mutagen 2018 Dec 11. Epub 2018 Dec 11.

Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana, United States of America, 47405.

At sites of chronic inflammation epithelial cells undergo aberrant DNA methylation that contributes to tumorigenesis. Inflammation is associated with an increase in reactive oxygen species (ROS) that cause oxidative DNA damage, which has also been linked to epigenetic alterations. We previously demonstrated that in response to ROS, mismatch repair (MMR) proteins MSH2 and MSH6 recruit epigenetic silencing proteins DNA methyltransferase 1 (DNMT1) and Polycomb repressive complex 2 (PRC2) members to sites of DNA damage, resulting in transcriptional repression of tumor suppressor genes (TSGs). Read More

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http://dx.doi.org/10.1002/em.22269DOI Listing
December 2018

Is chronic use of hydroxyurea safe for patients with sickle cell anemia? An account of genotoxicity and mutagenicity.

Environ Mol Mutagen 2018 Dec 7. Epub 2018 Dec 7.

Faculty of Pharmacy, Federal University of Ceará, Fortaleza, Brazil.

Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI) and chromosomal damage in leukocytes of adult patients with SCA with and without HU. The DI was assessed by the comet assay and chromosomal damage by the leukocyte micronucleus test of adult patients treated with HU (SCA-HU) and without the use of HU (SCA-NoHU). Read More

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http://dx.doi.org/10.1002/em.22260DOI Listing
December 2018

Understanding the importance of low-molecular weight (ethylene oxide- and propylene oxide-induced) DNA adducts and mutations in risk assessment: Insights from 15 years of research and collaborative discussions.

Environ Mol Mutagen 2018 Dec 10. Epub 2018 Dec 10.

University of North Carolina, Chapel Hill, North Carolina, USA.

The interpretation and significance of DNA adduct data, their causal relationship to mutations, and their role in risk assessment have been debated for many years. An extended effort to identify key questions and collect relevant data to address them was focused on the ubiquitous low MW N7-alkyl/hydroxyalkylguanine adducts. Several academic, governmental, and industrial laboratories collaborated to gather new data aimed at better understanding the role and potential impact of these adducts in quantifiable genotoxic events (gene mutations/micronucleus). Read More

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http://dx.doi.org/10.1002/em.22248DOI Listing
December 2018
1 Read

Effects of Acute Fluorene-9-Bisphenol Exposure on Mouse Oocyte in vitro Maturation and Its Possible Mechanisms.

Environ Mol Mutagen 2018 Nov 30. Epub 2018 Nov 30.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.

Fluorene-9-bisphenol (BHPF), a substitute of bisphenol A (BPA) used in the production of the so-called "BPA-free" plastics, has now been shown to be released from commercial plastic bottles into drinking water and has strong anti-estrogenic activity in mice, which suggests that BHPF is also an environmental toxin. However, whether BHPF exposure has effects on mouse oocyte development is unknown. In this study, the influence of acute exposure to BHPF (50-150 μM, 12 hr) on mouse oocyte maturation and its possible mechanisms were investigated. Read More

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http://dx.doi.org/10.1002/em.22258DOI Listing
November 2018
2.630 Impact Factor

LINE-1 Hypomethylation is Associated With Radiation-Induced Genomic Instability in Industrial Radiographers.

Environ Mol Mutagen 2018 Nov 29. Epub 2018 Nov 29.

School of Public Health, Seoul National University, Seoul, South Korea.

Global DNA hypomethylation is proposed as a potential biomarker for cancer risk associated with genomic instability, which is an important factor in radiation-induced cancer. However, the associations among radiation exposure, changes in DNA methylation, and carcinogenesis are unclear. The aims of this study were (1) to examine whether low-level occupational radiation exposure induces genomic DNA hypomethylation; and (2) to determine the relationships between radiation exposure, genomic DNA hypomethylation and radiation-induced genomic instability (RIGI) in industrial radiographers. Read More

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http://dx.doi.org/10.1002/em.22237DOI Listing
November 2018
3 Reads

Assessment of the Performance of the TGx-DDI Biomarker to Detect DNA Damage-Inducing Agents Using Quantitative RT-PCR in TK6 Cells.

Environ Mol Mutagen 2018 Nov 29. Epub 2018 Nov 29.

Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.

Gene expression biomarkers are now available for application in the identification of genotoxic hazards. The TGx-DDI transcriptomic biomarker can accurately distinguish DNA damage-inducing (DDI) from non-DDI exposures based on changes in the expression of 64 biomarker genes. The 64 genes were previously derived from whole transcriptome DNA microarray profiles of 28 reference agents (14 DDI and 14 non-DDI) after 4 h treatments of TK6 human lymphoblastoid cells. Read More

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http://dx.doi.org/10.1002/em.22257DOI Listing
November 2018

Mutagenicity of Ayahuasca and Their Constituents to the Salmonella/Microsome Assay.

Environ Mol Mutagen 2018 Nov 29. Epub 2018 Nov 29.

Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, São Paulo, Brazil.

Ayahuasca is a beverage used in religious rituals of indigenous and nonindigenous groups, and its therapeutic potential has been investigated. Ayahuasca is obtained by decoction of the Banisteriopsis caapi that contains β-carbolines (harmine, harmaline, and tetrahydroharmine) plus Psychotria viridis that contains N,N-dimethyltryptamine. Although plants used in folk medicine are recognized as safe, many of them have genotoxic potential. Read More

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http://dx.doi.org/10.1002/em.22263DOI Listing
November 2018
2 Reads

Leukocyte Telomere Length in Patients with Radiographic Knee Osteoarthritis.

Environ Mol Mutagen 2018 Nov 29. Epub 2018 Nov 29.

INIBIC-Complexo Hospitalario Universitario A Coruña (CHUAC), Genetics Unit, A Coruña, Spain.

Relative mean telomere sequence amount was determined by quantitative PCR (qPCR) of peripheral blood leukocyte (PBL) samples obtained at recruitment (n = 310) from individuals from the Osteoarthritis (OA) Initiative consortium. Knees were radiologically evaluated according to the Kellgren-Lawrence (KL) score, ranging from 0 to 4, considering a KL grade ≥ 2 as radiographic evidence of OA (n = 124). Telomere size decreased as baseline KL score increased, being significantly shorter in subjects with KL ≥2 (Mann-Whitney U-test, P < 0. Read More

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http://dx.doi.org/10.1002/em.22247DOI Listing
November 2018
3 Reads

Inhalation exposure to low levels of ethyl tertiary butyl ether: Its genetic effects were significantly modified by ALDH2 activity.

Environ Mol Mutagen 2018 Nov 25. Epub 2018 Nov 25.

National Institute of Occupational Safety and Health, Kawasaki, Japan.

Previous experiments showed that high concentrations of ethyl tertiary butyl ether (ETBE) exposure (500-5,000 ppm) significantly resulted in DNA damages in aldehyde dehydrogenase 2 (Aldh2) knockout (KO) mice. This study was aimed to verify the genotoxic effects in three genetic types, Aldh2 KO, heterogeneous (HT), and wild type (WT), of mice exposed to lower concentrations of ETBE (50-500 ppm) by inhalation. Histopathology assessments in the livers, measurements of genotoxic biomarkers in blood and livers, and urinary 8-hydroxydeoxyguanosion (8-OH-dG) for the oxidative DNA damage of whole body were performed. Read More

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http://dx.doi.org/10.1002/em.22256DOI Listing
November 2018

Exposure to the fungicide captan induces DNA base alterations and replicative stress in mammalian cells.

Environ Mol Mutagen 2018 Nov 24. Epub 2018 Nov 24.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.

The classification of the fungicide captan (CAS Number: 133-06-2) as a carcinogen agent is presently under discussion. Despite the mutagenic effect detected by the Ames test and carcinogenic properties observed in mice, the genotoxicity of this pesticide in humans is still unclear. New information is needed about its mechanism of action in mammalian cells. Read More

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http://dx.doi.org/10.1002/em.22268DOI Listing
November 2018
4 Reads
2.630 Impact Factor

The SOS System: A complex and tightly regulated response to DNA damage.

Environ Mol Mutagen 2018 Nov 16. Epub 2018 Nov 16.

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106, Warsaw, Poland.

Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. Read More

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http://doi.wiley.com/10.1002/em.22267
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http://dx.doi.org/10.1002/em.22267DOI Listing
November 2018
4 Reads

Cytome Micronucleus Assays with a Metabolically Competent Human Derived Liver Cell Line (Huh6): A Promising Approach for Routine Testing of Chemicals?

Environ Mol Mutagen 2018 Nov 8. Epub 2018 Nov 8.

Institute of Cancer Research, Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria.

One of the main problems of in vitro genotoxicity tests is the inadequate representation of drug metabolizing enzymes in most indicator cell lines which are currently used. We identified recently a human derived liver cell line (Huh6) which detected induction of DNA damage by representatives of different groups of promutagens without enzyme mix and showed that these cells are more suitable in terms of reproducibility and sensitivity as other currently used liver derived lines. We developed a protocol for micronucleus (MN) cytome assays with these cells and validated the procedure in experiments with representatives of different groups of directly and indirectly acting genotoxic carcinogens (MMS, cisplatin, PhIP, IQ, NDMA, B(a)P, AFB1, etoposide, and H O ). Read More

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http://doi.wiley.com/10.1002/em.22254
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http://dx.doi.org/10.1002/em.22254DOI Listing
November 2018
5 Reads

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating Their Spindle Assembly Checkpoint.

Environ Mol Mutagen 2018 Nov 7. Epub 2018 Nov 7.

School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Yunnan Normal University, Kunming, Yunnan, 650500, China.

Geraniin has been reported to specifically induce apoptosis in multiple human cancers, but the underlying mechanism is poorly defined. The spindle assembly checkpoint (SAC) is a surveillance system to ensure high-fidelity chromosome segregation during mitosis. Weakening of SAC to enhance chromosome instability (CIN) can be therapeutic because very high levels of CIN are lethal. Read More

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http://doi.wiley.com/10.1002/em.22265
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http://dx.doi.org/10.1002/em.22265DOI Listing
November 2018
2 Reads

Bioflavonoids promote stable translocations between MLL-AF9 breakpoint cluster regions independent of normal chromosomal context: Model system to screen environmental risks.

Environ Mol Mutagen 2018 Nov 2. Epub 2018 Nov 2.

Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, North Carolina.

Infant acute leukemias are aggressive and characterized by rapid onset after birth. The majority harbor translocations involving the MLL gene with AF9 as one of its most common fusion partners. MLL and AF9 loci contain breakpoint cluster regions (bcrs) with sequences hypothesized to be targets of topoisomerase II inhibitors that promote translocation formation. Read More

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http://doi.wiley.com/10.1002/em.22245
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http://dx.doi.org/10.1002/em.22245DOI Listing
November 2018
3 Reads

Mutagenic Activity of N-Nitrosodiethylamine in Cell Lines Expressing Human CYP2E1-Adequacy of Dimethylsulfoxide as Solvent.

Environ Mol Mutagen 2018 Nov 1. Epub 2018 Nov 1.

Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China.

Human CYP2E1 metabolizes many xenobiotics of low-molecular weight, thereby activating various promutagens/procarcinogens. In toxicological studies in vitro, dimethylsulfoxide (DMSO) is a common vehicle for organic compounds. However, it was observed to potently inhibit CYP2E1 activity. Read More

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http://doi.wiley.com/10.1002/em.22264
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http://dx.doi.org/10.1002/em.22264DOI Listing
November 2018
3 Reads

Genetic variation associated with chromosomal aberration frequency: A genome-wide association study.

Environ Mol Mutagen 2018 Oct 3. Epub 2018 Oct 3.

Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. Read More

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http://doi.wiley.com/10.1002/em.22236
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http://dx.doi.org/10.1002/em.22236DOI Listing
October 2018
13 Reads
2.630 Impact Factor

In vitro exposure to CPF affects bovine sperm epigenetic gene methylation pattern and the ability of sperm to support fertilization and embryo development.

Environ Mol Mutagen 2018 Oct 26. Epub 2018 Oct 26.

Dipartimento di Biologia, Università di Napoli Federico II, Naples, Italy.

Several studies have demonstrated that overexposure to pesticides can reduce mammalian sperm quality, impairing male fertility. Chlorpyrifos (CPF), a widely used organophosphate pesticide, was shown to impair spermatogenesis by inducing the formation of highly reactive toxic intermediates. To gain further insight into the mechanisms underlying the cytotoxicity and genotoxicity of CPF, bovine spermatozoa were exposed in vitro to environmental CPF concentrations and the motility, in vitro fertilization rates, DNA fragmentation, chromatin alterations, and methylation patterns were assessed. Read More

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http://doi.wiley.com/10.1002/em.22242
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http://dx.doi.org/10.1002/em.22242DOI Listing
October 2018
7 Reads

Evaluation of U. S. National Toxicology Program (NTP) mouse lymphoma assay data using International Workshop on Genotoxicity Tests (IWGT) and the Organization for Economic Co-Operation and Development (OECD) criteria.

Environ Mol Mutagen 2018 Dec 25;59(9):829-841. Epub 2018 Oct 25.

Ramboll, Little Rock, Arkansas.

The forward gene mutation mouse lymphoma assay (MLA) is widely used, as part of a regulatory test battery, to identify the genotoxic potential of chemicals. It identifies mutagens capable of inducing a variety of genetic events. During the 1980s and early 1990s, the U. Read More

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http://doi.wiley.com/10.1002/em.22250
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http://dx.doi.org/10.1002/em.22250DOI Listing
December 2018
5 Reads

Toxic and Genotoxic Effects of Silver Nanoparticles in Drosophila.

Environ Mol Mutagen 2018 Oct 24. Epub 2018 Oct 24.

Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.

The in vivo model Drosophila melanogaster was used here to determine the detrimental effects induced by silver nanoparticles (AgNPs) exposure. The main aim was to explore its interaction with the intestinal barrier and the genotoxic effects induced in hemocytes. The observed effects were compared with those obtained by silver nitrate, as an agent acting via the release of silver ions. Read More

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http://doi.wiley.com/10.1002/em.22262
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http://dx.doi.org/10.1002/em.22262DOI Listing
October 2018
5 Reads

In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses that Deplete Ovarian Follicles in Mice.

Environ Mol Mutagen 2018 Oct 24. Epub 2018 Oct 24.

Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, K1A 0K9, Canada.

Polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene (BaP) are ubiquitous environmental contaminants formed during incomplete combustion of organic materials. Our prior work showed that transplacental exposure to BaP depletes ovarian follicles and increases prevalence of epithelial ovarian tumors later in life. We used the MutaMouse transgenic rodent model to address the hypothesis that ovarian mutations play a role in tumorigenesis caused by prenatal exposure to BaP. Read More

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http://dx.doi.org/10.1002/em.22261DOI Listing
October 2018

Pilot studies evaluating the nongenotoxic rodent carcinogens phenobarbital and clofibrate in the rat Pig-a assay.

Environ Mol Mutagen 2018 Oct 19. Epub 2018 Oct 19.

Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.

The Pig-a assay is an emerging and promising in vivo method to determine mutagenic potential of chemicals. Since its development in 2008, remarkable progress has been made in harmonizing and characterizing the test procedures, primarily using known mutagenic chemicals. The purpose of the present study was to evaluate specificity of the Pig-a assay using two nongenotoxic and well-characterized rodent liver carcinogens, phenobarbital and clofibrate, in male F344/DuCrl rats. Read More

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http://dx.doi.org/10.1002/em.22232DOI Listing
October 2018

Using a gene expression biomarker to identify DNA damage-inducing agents in microarray profiles.

Environ Mol Mutagen 2018 Dec 17;59(9):772-784. Epub 2018 Oct 17.

Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.

High-throughput transcriptomic technologies are increasingly being used to screen environmental chemicals in vitro to provide mechanistic context for regulatory testing. The TGx-DDI biomarker is a 64-gene expression profile generated from testing 28 model chemicals or treatments (13 that cause DNA damage and 15 that do not) in human TK6 cells. While the biomarker is very accurate at predicting DNA damage inducing (DDI) potential using the nearest shrunken centroid method, the broad utility of the biomarker using other computational methods is not fully known. Read More

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http://doi.wiley.com/10.1002/em.22243
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http://dx.doi.org/10.1002/em.22243DOI Listing
December 2018
1 Read

Intestinal polycyclic aromatic hydrocarbon-DNA adducts in a population of beluga whales with high levels of gastrointestinal cancers.

Environ Mol Mutagen 2018 Oct 11. Epub 2018 Oct 11.

Canadian Wildlife Health Cooperative, Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, St. Hyacinthe, PQ, J2S2M2, Canada.

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) were disposed directly into the Saguenay River of the St. Lawrence Estuary (SLE) by local aluminum smelters (Quebec, Canada) for 50 years (1926-1976). PAHs in the river sediments are likely etiologically related to gastrointestinal epithelial cancers observed in 7% of 156 mature (>19-year old) adult beluga found dead along the shorelines. Read More

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http://doi.wiley.com/10.1002/em.22251
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http://dx.doi.org/10.1002/em.22251DOI Listing
October 2018
3 Reads

Gamma-H2AX immunofluorescence for the detection of tissue-specific genotoxicity in vivo.

Environ Mol Mutagen 2018 Oct 11. Epub 2018 Oct 11.

Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.

The phosphorylation of histone H2AX in Serine 139 (gamma-H2AX) marks regions of DNA double strand breaks and contributes to the recruitment of DNA repair factors to the site of DNA damage. Gamma-H2AX is used widely as DNA damage marker in vitro, but its use for genotoxicity assessment in vivo has not been extensively investigated. Here, we developed an image analysis system for the precise quantification of the gamma-H2AX signal, which we used to monitor DNA damage in animals treated with known genotoxicants (EMS, ENU and doxorubicin). Read More

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http://dx.doi.org/10.1002/em.22238DOI Listing
October 2018
7 Reads

Predictors of mitochondrial DNA copy number and damage in a mercury-exposed rural Peruvian population near artisanal and small-scale gold mining: An exploratory study.

Environ Mol Mutagen 2018 Oct 5. Epub 2018 Oct 5.

Nicholas School of the Environment, Duke University, Durham, North Carolina.

Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood cells have been proposed as effect biomarkers for pollutant exposures. Studies have shown that mercury accumulates in mitochondria and affects mitochondrial function and integrity; however, these data are derived largely from experiments in model systems, rather than human population studies that evaluate the potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and damage in white blood cells (WBCs) from 83 residents of nine communities in the Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal and small-scale gold mining. Read More

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http://doi.wiley.com/10.1002/em.22244
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http://dx.doi.org/10.1002/em.22244DOI Listing
October 2018
2 Reads

Micronuclei frequency in urothelial cells of bladder cancer patients, as a biomarker of prognosis.

Environ Mol Mutagen 2018 Oct 4. Epub 2018 Oct 4.

Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193, Barcelona, Spain.

It has been suggested that the frequency of micronuclei (MN) in defoliated urothelial cells could be used as a biomarker for both the potential risk of bladder cancer (BC) and its progression. To prove this we have carried out a large study evaluating the MN frequency in a group of 383 hospital patients submitted to cystoscopy. From them, 77 were negative in their first cystoscopy, and were considered as a reference group; 79 were positive and were classified as patients with tumor; and 227 with previous bladder cancer submitted to follow-up monitoring were negative and classified as BC patients without tumor. Read More

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http://doi.wiley.com/10.1002/em.22252
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http://dx.doi.org/10.1002/em.22252DOI Listing
October 2018
6 Reads

Sleeping beauty transposon-mediated poly(A)-trapping and insertion mutagenesis in mouse embryonic stem cells.

Environ Mol Mutagen 2018 Oct 2;59(8):687-697. Epub 2018 Oct 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Saturation mutagenesis of all endogenous genes within the mouse genome remains a challenging task, although a plenty of gene-editing approaches are available for this purpose. Here, a poly(A)-trap vector was generated for insertion mutagenesis in mouse embryonic stem (mES) cells. This vector contains an expression cassette of neomycin (Neo)-resistant gene lacking a poly(A) signal and flanked by two inverted terminal repeats of the Sleeping Beauty (SB) transposon. Read More

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http://doi.wiley.com/10.1002/em.22234
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http://dx.doi.org/10.1002/em.22234DOI Listing
October 2018
2 Reads

Suitability of Long-Term Frozen Rat Blood Samples for the Interrogation of Pig-a Gene Mutation by Flow Cytometry.

Environ Mol Mutagen 2018 Sep 27. Epub 2018 Sep 27.

Litron Laboratories, Rochester, New York.

The rodent blood Pig-a assay has been undergoing international validation for use as an in vivo hematopoietic cell gene mutation assay, and given the promising results an Organization for Economic Co-operation and Development (OECD) Test Guideline is currently under development. Enthusiasm for the assay stems in part from its alignment with 3Rs principles permitting combination with other genotoxicity endpoint(s) and integration into repeat-dose toxicology studies. One logistical requirement and experimental design limitation has been that blood samples required antibody labeling and flow cytometric analysis within one week of collection. Read More

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http://doi.wiley.com/10.1002/em.22249
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http://dx.doi.org/10.1002/em.22249DOI Listing
September 2018
3 Reads

Cytokinesis Block Micronucleus Cytome (CBMN Cyt) Assay Biomarkers and Their Association With Radiation Sensitivity Phenotype in Prostate Cancer Cases and DNA Repair Gene hOGG1 (C1245G) Polymorphism.

Environ Mol Mutagen 2018 Dec 27;59(9):813-821. Epub 2018 Sep 27.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.

Prostate cancer (PC) is commonly diagnosed cancer in men but only a few risk factors, such as family history, ethnicity, and age have been established. Chromosomal instability is another possible risk factor but this has not been adequately explained previously. In this study, we tested the hypotheses that peripheral blood lymphocytes (PBL) of PC patients have (1) an abnormally high level of chromosomal instability; (2) that they are hypersensitive to ionizing radiation-induced DNA damage; and (3) that these phenotypes are affected by hOGG1 (C1245G) polymorphism. Read More

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http://dx.doi.org/10.1002/em.22240DOI Listing
December 2018

Chromosome Missegregation and Aneuploidy Induction in Human Peripheral Blood Lymphocytes In vitro by Low Concentrations of Chlorpyrifos, Imidacloprid and α-Cypermethrin.

Environ Mol Mutagen 2018 Sep 27. Epub 2018 Sep 27.

Unit of Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.

Chlorpyrifos, imidacloprid, and α-cypermethrin are some of the most widely used insecticides in contemporary agriculture. However, their low-dose, nontarget genotoxic effects have not been extensively assayed. As one of the most relevant cancer biomarkers, we aimed to assess the aneuploidy due to chromosome missegregation during mitosis. Read More

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http://doi.wiley.com/10.1002/em.22235
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http://dx.doi.org/10.1002/em.22235DOI Listing
September 2018
4 Reads

Genomic chaos in peripheral blood lymphocytes of Hodgkin's lymphoma patients one year after ABVD chemotherapy/radiotherapy.

Environ Mol Mutagen 2018 Oct 8;59(8):755-768. Epub 2018 Sep 8.

Laboratorio de Citogenética, Instituto Nacional de Pediatría, Ciudad de México, Mexico.

Hodgkin's lymphoma (HL) is a lymphoid malignancy representing 5% of all cancers in children, 16% in adolescents, and 30-40% of all malignant lymphomas and has a survival rate of ~95% at 10 years. One of the most common treatment schemes uses a cocktail of genotoxic agents including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy. We investigated the occurrence of chromosomal damage in peripheral blood lymphocytes from five patients diagnosed with HL who provided samples before (BT), during chemotherapy (DT) and ~1 year after ABVD chemotherapy/radiotherapy (AT). Read More

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http://dx.doi.org/10.1002/em.22216DOI Listing
October 2018
1 Read

Lifespan Kras mutation levels in lung and liver of B6C3F mice.

Environ Mol Mutagen 2018 Oct 26;59(8):715-721. Epub 2018 Sep 26.

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas.

Somatic mutations accumulate in the human genome and are correlated with increased cancer incidence as humans age. The standard model for studying the carcinogenic effects of exposures for human risk assessment is the rodent 2-year carcinogenicity assay. However, there is little information regarding the effect of age on cancer-driver gene mutations in these models. Read More

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http://dx.doi.org/10.1002/em.22198DOI Listing
October 2018

Interactions between superoxide dismutase and paraoxonase polymorphic variants in nonsyndromic cleft lip with or without cleft palate in the Brazilian population.

Environ Mol Mutagen 2018 Sep 21. Epub 2018 Sep 21.

Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.

During development, oxidative stress is hypothesized to mediate embryotoxicity, which may be intensified by exposition to environmental factors and by genetic variations in the enzymes involved in protecting cells from these damaging effects, including superoxide dismutase (SOD) and paraoxonase (PON). The aim of this study was to evaluate the influence of single-nucleotide polymorphisms (SNP) in genes associated with the neutralization of oxidative stress (SOD and PON family members) in the risk of nonsyndromic oral cleft in the Brazilian population. Initially, we tested for association between 28 SNP in SOD1, SOD2, SOD3, PON1, PON2, and PON3 among 325 nonsyndromic cleft lip with or without cleft palate (NSCL±P) case-parent trios. Read More

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http://dx.doi.org/10.1002/em.22239DOI Listing
September 2018
2.630 Impact Factor

Assessment of the Pig-a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate.

Environ Mol Mutagen 2018 Sep 21. Epub 2018 Sep 21.

Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.

The utility and sensitivity of the newly developed flow cytometric Pig-a gene mutation assay have become a great concern recently. In this study, we have examined the feasibility of integrating the Pig-a assay as well as micronucleus and Comet endpoints into acute and subchronic general toxicology studies. Male Sprague-Dawley rats were treated for 3 or 28 consecutive days by oral gavage with procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum tolerated dose. Read More

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http://dx.doi.org/10.1002/em.22227DOI Listing
September 2018
2 Reads
2.630 Impact Factor

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet.

Environ Mol Mutagen 2018 Oct 19;59(8):742-754. Epub 2018 Sep 19.

Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse, France.

Through diet, people are exposed simultaneously to a variety of contaminants (e.g. heavy metals, mycotoxins, pesticides) that could have combined adverse effects on human health. Read More

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http://dx.doi.org/10.1002/em.22214DOI Listing
October 2018

Effects of hydroxyurea on CNV induction in the mouse germline.

Environ Mol Mutagen 2018 Oct 15;59(8):698-714. Epub 2018 Sep 15.

Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.

Copy number variants (CNVs) are important in genome variation and genetic disease, with new mutations arising frequently in the germline and somatic cells. Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer of de novo CNVs in cultured mammalian cells. HU is used extensively for long-term management of sickle cell disease. Read More

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http://dx.doi.org/10.1002/em.22233DOI Listing
October 2018
6 Reads

Assessment of the mutagenic potential of para-chloroaniline and aniline in the liver, spleen, and bone marrow of Big Blue® rats with micronuclei analysis in peripheral blood.

Environ Mol Mutagen 2018 Dec 14;59(9):785-797. Epub 2018 Sep 14.

MilliporeSigma, BioReliance® Toxicology Testing Services, Rockville, Maryland.

Splenic tumors have been reported in rat cancer bioassays with para-chloroaniline (PCA) and aniline. Development of these tumors is hypothesized to be due to hematotoxicity via the formation of methemoglobin (MetHb) and not direct DNA reactivity. To evaluate the mode of action (MOA) for tumor formation a transgenic rodent (TGR) in vivo gene mutation assay in Big Blue® TgF344 rats was performed with parallel micronuclei analysis in peripheral blood. Read More

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http://doi.wiley.com/10.1002/em.22241
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http://dx.doi.org/10.1002/em.22241DOI Listing
December 2018
9 Reads

Somatic mutation load and spectra: A record of DNA damage and repair in healthy human cells.

Environ Mol Mutagen 2018 Oct 27;59(8):672-686. Epub 2018 Aug 27.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of Health, Durham, North Carolina.

Somatic genome instability is a hallmark of cancer genomes and has been linked to aging and a variety of other pathologies. Large-scale cancer genome and exome sequencing have revealed that mutation load and spectra in cancers can be influenced by environmental exposures, the anatomical site of exposures, and tissue type. There is now an abundance of data favoring the hypothesis that a substantial portion of the mutations in cancers originate prior to carcinogenesis in stem cells of the healthy individual. Read More

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http://dx.doi.org/10.1002/em.22215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188803PMC
October 2018
1 Read
2.630 Impact Factor

In Vivo genotoxicity of a commercial C.I. Disperse Red 1 dye.

Environ Mol Mutagen 2018 Dec 27;59(9):822-828. Epub 2018 Aug 27.

Department of Pathology, Medical School, São Paulo State University, Botucatu, São Paulo, Brazil.

Color Index (C.I.) Disperse Red 1 (DR1) is a widely used textile azo dye found in rivers. Read More

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http://dx.doi.org/10.1002/em.22226DOI Listing
December 2018

In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water.

Environ Mol Mutagen 2018 Aug;59(7):586-594

Radiobiology and Health, Canadian Nuclear Laboratories, Chalk-River, ON, Canada.

Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it. Read More

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http://dx.doi.org/10.1002/em.22200DOI Listing
August 2018
1 Read

Meiotic arrest and spindle defects are associated with altered KIF11 expression in porcine oocytes.

Environ Mol Mutagen 2018 Dec 28;59(9):805-812. Epub 2018 Aug 28.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Kinesin superfamily proteins (KIFs) act as molecular motors and are involved in material transport along microtubules to maintain normal cellular functions. KIF11 (also named kinesin-5, Eg5, and KSP) is a plus-end-directed homotetrameric kinesin that regulates spindle formation for actuate chromosomal separation during mitosis. However, the roles of KIF11 in meiosis are still unclear. Read More

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http://doi.wiley.com/10.1002/em.22213
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http://dx.doi.org/10.1002/em.22213DOI Listing
December 2018
3 Reads

Global metabolomic responses in urine from atm deficient mice in response to LD gamma irradiation doses.

Environ Mol Mutagen 2018 Aug 10;59(7):576-585. Epub 2018 Aug 10.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.

Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm in the C57BL/6 background, and evaluated the urinary responses in 8-10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD doses [4 Gy for Atm , and 8 Gy for wild type (WT)]. Read More

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http://dx.doi.org/10.1002/em.22202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113093PMC

Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India.

Environ Mol Mutagen 2018 Aug 9;59(7):653-667. Epub 2018 Aug 9.

Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India.

Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1β and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Read More

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http://dx.doi.org/10.1002/em.22208DOI Listing
August 2018
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Analysis of mutation in the rat Pig-a assay: I) studies with bone marrow erythroid cells.

Environ Mol Mutagen 2018 Oct 9;59(8):722-732. Epub 2018 Aug 9.

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas.

We have established a flow cytometry-based Pig-a assay for rat bone marrow erythroid cells (BMEs). The BME Pig-a assay uses a DNA-specific stain and two antibodies: one against the transmembrane transferrin receptor (CD71 marker) and the other against the GPI-anchored complement inhibitory protein (CD59 marker). In F344 male rats treated acutely with a total of 120 mg/kg of N-ethyl-N-nitrosourea (ENU) the frequency of CD59-deficient phenotypically mutant BMEs increased approximately 24-fold compared to the rats concurrently treated with the vehicle. Read More

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http://dx.doi.org/10.1002/em.22211DOI Listing
October 2018
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Caenorhabditis elegans as an emerging model system in environmental epigenetics.

Environ Mol Mutagen 2018 Aug 9;59(7):560-575. Epub 2018 Aug 9.

Institute for Society and Genetics, University of California at Los Angeles, Los Angeles, California.

The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. Read More

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http://dx.doi.org/10.1002/em.22203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113102PMC
August 2018
5 Reads

Analysis of mutation in the rat Pig-a assay: II. Studies with bone marrow granulocytes.

Environ Mol Mutagen 2018 Oct 9;59(8):733-741. Epub 2018 Aug 9.

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas.

The in vivo erythrocyte Pig-a gene mutation assay measures the phenotypic loss of GPI-anchored surface markers. Molecular analysis of the marker-deficient erythrocytes cannot provide direct proof that the mutant phenotype is due to mutation in the Pig-a gene because mammalian erythrocytes lack genomic DNA. Granulocytes are nucleated cells that originate from myeloid progenitor cells in bone marrow as is the case for erythrocytes, and thus analysis of Pig-a mutation in bone marrow granulocytes can provide information about the source of mutations detected in the erythrocyte Pig-a assay. Read More

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http://dx.doi.org/10.1002/em.22210DOI Listing
October 2018

Validation of Gelbond® high-throughput alkaline and Fpg-modified comet assay using a linear mixed model.

Environ Mol Mutagen 2018 Aug 9;59(7):595-602. Epub 2018 Aug 9.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.

Even if the comet assay has been widely used for decades, there is still a need for controlled studies and good mathematical models to assess the variability of the different versions of this assay and in particular to assess potential intra-experimental variability of the high-throughput comet assay. To address this point, we further validate a high-throughput comet assay that uses hydrophilic polyester film (Gelbond®). Experiments were performed using human peripheral blood mononuclear cells (PBMC) either untreated or treated with different concentration of MMS (methyl methanesulfonate). Read More

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http://dx.doi.org/10.1002/em.22204DOI Listing

2,4-Dichlorophenol induces DNA damage through ROS accumulation and GSH depletion in goldfish Carassius auratus.

Environ Mol Mutagen 2018 Dec 9;59(9):798-804. Epub 2018 Aug 9.

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.

2,4-Dichlorophenol (2,4-DCP) is one of the most abundant chlorophenols in the aquatic environment and has been frequently detected in surface waters. Although ecological and cellular toxicity of 2,4-DCP has aroused the public concern, few reports focus on the genotoxicity, especially on DNA double strand breaks (DSBs), of 2,4-DCP in fish. The present study aims to explore the genotoxic effect of 2,4-DCP on DSBs in goldfish Carassius auratus and to further elucidate its potential mechanism. Read More

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http://dx.doi.org/10.1002/em.22209DOI Listing
December 2018
3 Reads

Loss of DNA polymerase β induces cellular senescence.

Environ Mol Mutagen 2018 Aug 3;59(7):603-612. Epub 2018 Jul 3.

Department of Nutrition and Food Science, Wayne State University, Detroit, Michigan.

We aim to establish that accelerated aging and premature cellular senescence seen in individuals with Down syndrome is related to reduced DNA polymeraseβ. We report here that primary fibroblasts from Down syndrome individuals exhibit greater SA-β-gal staining (fourfold increase, P < 0.001), increased p16 transcript abundance (threefold increase, P < 0. Read More

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http://dx.doi.org/10.1002/em.22206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203593PMC
August 2018
2 Reads