Perinatal lead (Pb) exposure results in sex and tissue ‐dependent adult DNA methylation alterations in murine IAP transposons
Epidemiological and animal data suggest that adult chronic disease is influenced by early‐life exposure‐induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic‐ and activity‐related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human ...
Source: Environmental and Molecular Mutagenesis - August 19, 2017 Category: Molecular Biology Authors: L. Montrose, C. Faulk, J. Francis, D.C. Dolinoy Tags: Research Article Source Type: research

DNA damage in kidney transplant patients. Role of organ origin
Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. F...
Source: Environmental and Molecular Mutagenesis - August 19, 2017 Category: Molecular Biology Authors: Zuray Corredor, Lara Rodr íguez‐Ribera, Elisabet Coll, Irene Silva, Juan Manuel Díaz, José Ballarín, Ricard Marcos, Susana Pastor Tags: Research Article Source Type: research

Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia
Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL. SUV...
Source: Environmental and Molecular Mutagenesis - August 19, 2017 Category: Molecular Biology Authors: Juliana Carvalho Alves ‐Silva, Doralina do Amaral Rabello, Martha Oliveira Bravo, Antônio Roberto Lucena‐Araujo, Diego Madureira de Oliveira, Fábio Morato de Oliveira, Eduardo Magalhaes Rego, Fábio Pittella‐Silva, Felipe Saldanha‐Araujo Tags: Research Article Source Type: research

In vivo pig ‐a and micronucleus study of the prototypical aneugen vinblastine sulfate
The Pig‐a assay is being used in regulatory studies to evaluate the potential of agents to induce somatic cell gene mutations and an OECD test guideline is under development. A working group involved with establishing the guideline recently noted that representative aneugenic agents had not been evaluated, and to help fill this data gap Pig‐a mutant phenotype and micronucleated reticulocyte frequencies were measured in an integrated study design to assess the mutagenic and cytogenetic damage responses to vinblastine sulfate exposure. Male Sprague Dawley rats were treated for twenty‐eight consecutive days with vinblas...
Source: Environmental and Molecular Mutagenesis - August 19, 2017 Category: Molecular Biology Authors: Svetlana L. Avlasevich, Carson Labash, Dorothea K. Torous, Jeffrey C. Bemis, James T. MacGregor, Stephen D. Dertinger Tags: Research Article Source Type: research

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(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - August 14, 2017 Category: Molecular Biology Tags: Issue Information Source Type: research

The TGx ‐28.65 biomarker online application for analysis of transcriptomics data to identify DNA damage‐inducing chemicals in human cell cultures
The TGx‐28.65 biomarker is a 65‐gene expression profile generated from testing 28 model chemicals (13 that cause DNA damage and 15 that do not) in human TK6 cells. It is used to predict whether a chemical induces DNA damage or not. We expanded availability to the biomarker by developing the online TGx‐28.65 biomarker application for predicting the DNA damage inducing (DDI) potential of suspect toxicants tested in p53‐proficient human cells and assessing putative mode(s) of action (MOA). Applications like this that analyse gene expression data to predict the hazard potential of test chemicals hold great promise for ...
Source: Environmental and Molecular Mutagenesis - August 2, 2017 Category: Molecular Biology Authors: Marcus A. Jackson, Longlong Yang, Isabel Lea, Asif Rashid, Byron Kuo, Andrew Williams, Carole Lyn Yauk, Jennifer Fostel Tags: Brief Communication Source Type: research

Effects of fluoride on morphology, growth, development, and thyroid hormone of Chinese toad (Bufo gargarizans) embryos
Excessive fluoride in natural water ecosystem has the potential to detrimentally affect amphibians, but little is known of such effects or underlying mechanisms in Bufo gargarizans embryos. In the present study, the effects of fluoride exposure on B. gargarizans embryos were investigated. First, fluoride teratogenic experiment showed that the 9 days EC50 of fluoride on B. gargarizans embryos was 177.62 mg/L. Then, we studied the sublethal effects of fluoride on B. gargarizans embryos at control, 0.7, 4.1, 19.6, 41.9, and 62.7 mg/L fluoride concentration. Malformation, growth, and development of embryos were monitored, an...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Yuhui Zhang, Lei Xie, Xinyi Li, Lihong Chai, Mengxing Chen, Xiaojing Kong, Qingqing Wang, Jingfei Liu, Lijuan Zhi, Chang Yang, Hongyuan Wang Tags: Research Article Source Type: research

Genotoxicity of airborne PM2.5 assessed by salmonella and comet assays in five cities of the Emilia ‐Romagna (Italy) mutagenicity monitoring network
In this study we evaluate and compare mutagenic and genotoxic potencies of PM2.5 collected in three seasons, from 2012 to 2015, in five Italian cities. Mutagenicity was evaluated through the Ames test on TA98 and TA100 strains and, for the measurement of PM clastogenicity, Comet assay was carried out on cultured human lung cells (A549). Organic matter, extracted from urban particulate matter, was also characterized for polycyclic aromatic hydrocarbons (PAHs) and their derivatives content. Samples collected in the colder seasons show the presence of both base pair substitution and frameshift mutagens, with enhanced mutageni...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Clara Bocchi, Cristina Bazzini, Federica Fontana, Giancarlo Pinto, Francesca Cassoni Tags: Research Article Source Type: research

Thiopurine ‐induced mitotic catastrophe in Rad51d‐deficient mammalian cells
Thiopurines are part of a clinical regimen used for the treatment of autoimmune disorders and childhood acute lymphoblastic leukemia. However, despite these successes, there are also unintended consequences such as therapy‐induced cancer in long‐term survivors. Therefore, a better understanding of cellular responses to thiopurines will lead to improved and personalized treatment strategies. RAD51D is an important component of homologous recombination (HR), and our previous work established that mammalian cells defective for RAD51D are more sensitive to the thiopurine 6‐thioguanine (6TG) and have dramatically increase...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Michael D. Wyatt, Nicole M. Reilly, Shikha Patel, Preeti Rajesh, Gary P. Schools, Phillip G. Smiraldo, Douglas L. Pittman Tags: Research Article Source Type: research

Classification of in vitro genotoxicants using a novel multiplexed biomarker assay compared to the flow cytometric micronucleus test
Regulatory in vitro genotoxicity testing exhibits shortcomings in specificity and mode of action (MoA) information. Thus, the aim of this work was to evaluate the performance of the novel MultiFlow® assay composed of mechanistic biomarkers quantified in TK6 cells after treatment (4 and 24 hr): γH2AX (DNA double strand breaks), phosphorylated H3 (mitotic cells), translocated p53 (genotoxicity), and cleaved PARP1 (apoptosis). A reference dataset of 31 compounds with well‐established MoA was studied using the MicroFlow® micronucleus assay. A positive call was raised following the earlier published criteria from Litron La...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Sabrina Wilde, Miriam Dambowsky, Claudia Hempt, Andreas Sutter, Nina Queisser Tags: Research Article Source Type: research

Tissue ‐specific and time‐dependent clonal expansion of ENU‐induced mutant cells in gpt delta mice
In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N‐ethyl‐N‐nitrosourea (ENU) with the persistence of ENU‐induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment. The gpt mutations were passengers of the mutant cell of origin and its daughter cells and thus could be used as neutral markers of clones that arose and persisted in the tissues. Female B6C3F1 mice exposed for 1 month to 200 ppm ENU in the d...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Takafumi Nakayama, Tomoko Sawai, Ikuko Masuda, Shinya Kaneko, Kazumi Yamauchi, Benjamin J. Blyth, Yoshiya Shimada, Akira Tachibana, Shizuko Kakinuma Tags: Research Article Source Type: research

Micronuclei and other erythrocyte nuclear abnormalities in fishes from the Great Lakes Basin, USA
This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Ryan P. Braham, Vicki S. Blazer, Cassidy H. Shaw, Patricia M. Mazik Tags: Research Article Source Type: research

Time ‐ and concentration‐dependent genomic responses of the rat airway to inhaled nickel sulfate
While insoluble nickel subsulfide (Ni3S2) was carcinogenic in the lung in a 2‐year rat bioassay, soluble nickel sulfate hexahydrate (NiSO4*6H2O) was not. To investigate whether differences in the cellular responses to these two nickel compounds could underlie their differential activities, we conducted parallel studies to determine the gene expression changes in micro‐dissected lung distal airway cells from Fischer 344 rats following inhalation of the two compounds for one and four weeks (6 hr per day, 5 days per week). The results of the Ni3S2 study have been reported previously; this paper reports the results for NiS...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: A. Y. Efremenko, J. L. Campbell, D. E. Dodd, A. R. Oller, H. J. Clewell Tags: Research Article Source Type: research

Genotoxic effects of high dose rate X ‐ray and low dose rate gamma radiation in ApcMin/+ mice
Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mic...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Anne Graupner, Dag M. Eide, Dag A. Brede, Michele Ellender, Elisabeth Lindbo Hansen, Deborah H. Oughton, Simon D. Bouffler, Gunnar Brunborg, Ann Karin Olsen Tags: Research Article Source Type: research

Bcl ‐2 protects TK6 cells against hydroquinone‐induced apoptosis through PARP‐1 cytoplasm translocation and stabilizing mitochondrial membrane potential
This study aimed to investigate the role of Bcl‐2 in controlling the mitochondrial pathway of apoptosis during hydroquinone (HQ)‐induced TK6 cytotoxicity. In this study, HQ, one metabolite of benzene, decreased the MMP in a concentration‐dependent manner and induced the generation of reactive oxygen species (ROS), the activation of the DNA damage marker γ‐H2AX, and production of the DNA damage‐responsive enzyme poly(ADP‐ribose)polymerase‐1 (PARP‐1). Exposure of TK6 cells to HQ leads to an increase in Bcl‐2 and co‐localization with PARP‐1 in the cytoplasm. Inhibition of Bcl‐2 using the BH3 mimetic, ...
Source: Environmental and Molecular Mutagenesis - August 1, 2017 Category: Molecular Biology Authors: Yuting Chen, Shaoyun Chen, Hairong Liang, Hui Yang, Linhua Liu, Kairu Zhou, Longmei Xu, Jiaxian Liu, Lin Yun, Bei Lai, Li Song, Hao Luo, Jianming Peng, Zhidong Liu, Yongmei Xiao, Wen Chen, Huanwen Tang Tags: Research Article Source Type: research