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Environmental and Molecular Mutagenesis

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https://www.readbyqxmd.com/read/29968395/loss-of-dna-polymerase-%C3%AE-induces-cellular-senescence
#1
Aqila A Ahmed, Cristine Smoczer, Brianna Pace, David Patterson, Diane Cress Cabelof
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 < 0.01), and reduced HMGB1 nuclear localization (1.5-fold lower, P < 0.01). We also find that DNA polymerase β expression is significantly reduced in Down syndrome primary fibroblasts (53% decline, P < 0...
July 3, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29968392/hepatic-dna-damage-in-harbour-porpoises-phocoena-phocoena-stranded-along-the-english-and-welsh-coastlines
#2
Karina Acevedo-Whitehouse, Kathy J Cole, David H Phillips, Paul D Jepson, Rob Deaville, Volker M Arlt
One level at which persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons PAHs) can exert damage is by causing DNA strand-breaks or nucleotide base modifications, which, if unrepaired, can lead to embryonic mutations, abnormal development and cancer. In marine ecosystems, genotoxicity is expected to be particularly strong in long-lived apex predators due to pollutant bioaccumulation. We conducted 32 P-postlabeling analyses optimized for the detection and quantification of aromatic/hydrophobic DNA adducts in the livers of 40 sexually-mature North Atlantic harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines...
July 3, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29968258/oxidative-stress-index-is-increased-in-children-exposed-to-industrial-discharges-and-is-inversely-correlated-with-metabolite-excretion-of-voc
#3
Rocío López-Vargas, Alejandra Méndez-Serrano, Arnulfo Albores-Medina, Fernando Oropeza-Hernández, Leticia Hernández-Cadena, Franciso Mercado-Calderón, Esmeralda Alvarado-Toledo, Selene Herrera-Morales, Omar Arellano-Aguilar, Guadalupe García-Vargas, Regina Montero-Montoya
Although the Atoyac River has been classified as highly polluted by environmental authorities, several communities are settled on its banks, affecting around 1.5 million persons, as well as farmland, due to an environmental distribution of toxics in the area. Our aim was to demonstrate that this environment affects important physiological processes that have an impact in health, so we conducted a study of schoolchildren from small communities on the banks of the river and in another similar town located far from it...
July 3, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29761935/the-application-of-transcriptional-benchmark-dose-modeling-for-deriving-thresholds-of-effects-associated-with-solar-simulated-ultraviolet-radiation-exposure
#4
Sami S Qutob, Vinita Chauhan, Byron Kuo, Andrew Williams, Carole L Yauk, James P McNamee, B Gollapudi
Considerable data has been generated to elucidate the transcriptional response of cells to ultraviolet radiation (UVR) exposure providing a mechanistic understanding of UVR-induced cellular responses. However, using these data to support standards development has been challenging. In this study, we apply benchmark dose (BMD) modeling of transcriptional data to derive thresholds of gene responsiveness following exposure to solar-simulated UVR. Human epidermal keratinocytes were exposed to three doses (10, 20, 150 kJ/m2 ) of solar simulated UVR and assessed for gene expression changes 6 and 24 hr postexposure...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29761929/assessment-of-polycyclic-aromatic-hydrocarbon-exposure-lung-function-systemic-inflammation-and-genotoxicity-in-peripheral-blood-mononuclear-cells-from-firefighters-before-and-after-a-work-shift
#5
Maria Helena Guerra Andersen, Anne Thoustrup Saber, Julie Elbaek Pedersen, Peter Bøgh Pedersen, Per Axel Clausen, Mille Løhr, Ali Kermanizadeh, Steffen Loft, Niels E Ebbehøj, Åse Marie Hansen, Ismo Kalevi Koponen, Eva-Carina Nørskov, Ulla Vogel, Peter Møller
Firefighting is regarded as possibly carcinogenic, although there are few mechanistic studies on genotoxicity in humans. We investigated exposure to polycyclic aromatic hydrocarbons (PAH), lung function, systemic inflammation and genotoxicity in peripheral blood mononuclear cells (PBMC) of 22 professional firefighters before and after a 24-h work shift. Exposure was assessed by measurements of particulate matter (PM), PAH levels on skin, urinary 1-hydroxypyrene (1-OHP) and self-reported participation in fire extinguishing activities...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29761860/hypermethylation-of-cpg-islands-is-associated-with-increasing-chromosomal-damage-in-chinese-lead-exposed-workers
#6
Li-Bo Yu, Yu-Ting Tu, Jing-Wen Huang, Ya-Nan Zhang, Guo-Qiao Zheng, Xiao-Wen Xu, Jin-Wei Wang, Jean Qin Xiao, David C Christiani, Zhao-Lin Xia
Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29761828/differential-micronucleus-frequency-in-isogenic-human-cells-deficient-in-dna-repair-pathways-is-a-valuable-indicator-for-evaluating-genotoxic-agents-and-their-genotoxic-mechanisms
#7
Liton Kumar Saha, Sujin Kim, Habyeong Kang, Salma Akter, Kyungho Choi, Tetsushi Sakuma, Takashi Yamamoto, Hiroyuki Sasanuma, Kouji Hirota, Jun Nakamura, Masamitsu Honma, Shunichi Takeda, S Dertinger
The micronucleus (MN) test has become an attractive tool both for evaluating the genotoxicity of test chemicals because of its ability to detect clastogenic and aneugenic events and for its convenience. As the MN assay has been mostly performed using only DNA repair-proficient mammalian cells, we believed that the comparison of the MN frequency between DNA repair-proficient and -deficient human cells may be an excellent indicator for detecting the genotoxic potential of test chemicals and for understanding their mode of action...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29536573/application-of-the-cometchip-platform-to-assess-dna-damage-in-field-collected-blood-samples-from-turtles
#8
Peter Sykora, Ylenia Chiari, Andrew Heaton, Nickolas Moreno, Scott Glaberman, Robert W Sobol
DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism-induced oxidative damage that can lead to single-strand and double-strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra-violet light, can also contribute to exogenously derived DNA damage...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29481708/2-hydroxypyridine-n-oxide-hopo-equivocal-in-the-ames-assay
#9
Krista L Dobo, Jennifer R Cheung, William C Gunther, Michelle O Kenyon
2-Hydroxypyridine-N-oxide (HOPO) is a useful coupling reagent for synthesis of active pharmaceutical ingredients. It has been reported to be weakly mutagenic in the Ames assay (Ding W et al. []: J Chromatogr A 1386:47-52). According to the ICH M7 guidance (2014) regarding control of mutagenic impurities to limit potential carcinogenic risk, mutagens require control in drug substances such that exposure not exceeds the threshold of toxicological concern. Given the weak response observed in the Ames assay and the lack of any obvious structural features that could confer DNA reactivity we were interested to determine if the results were reproducible and investigate the role of potentially confounding experimental parameters...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29481700/conventional-and-novel-omics-based-approaches-to-the-study-of-carbon-nanotubes-pulmonary-toxicity
#10
REVIEW
Célia Ventura, António Sousa-Uva, João Lavinha, Maria João Silva
The widespread application of carbon nanotubes (CNT) on industrial, biomedical, and consumer products can represent an emerging respiratory occupational hazard. Particularly, their similarity with the fiber-like shape of asbestos have raised a strong concern about their carcinogenic potential. Several in vitro and in vivo studies have been supporting this view by pointing to immunotoxic, cytotoxic and genotoxic effects of some CNT that may conduct to pulmonary inflammation, fibrosis, and bronchioloalveolar hyperplasia in rodents...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29417643/high-throughput-image-cytometry-micronucleus-assay-to-investigate-the-presence-or-absence-of-mutagenic-effects-of-cold-physical-plasma
#11
Sander Bekeschus, Anke Schmidt, Axel Kramer, Hans-Robert Metelmann, Frank Adler, Thomas von Woedtke, Felix Niessner, Klaus-Dieter Weltmann, Kristian Wende
Promising cold physical plasma sources have been developed in the field of plasma medicine. An important prerequisite to their clinical use is lack of genotoxic effects in cells. During optimization of one or even different plasma sources for a specific application, large numbers of samples need to be analyzed. There are soft and easy-to-assess markers for genotoxic stress such as phosphorylation of histone H2AX (γH2AX) but only few tests are accredited by the OECD with regard to mutagenicity detection. The micronucleus (MN) assay is among them but often requires manual counting of many thousands of cells per sample under the microscope...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29399883/dna-damage-induced-apoptosis-and-mitogen-activated-protein-kinase-pathway-contribute-to-the-toxicity-of-dronedarone-in-hepatic-cells
#12
Si Chen, Zhen Ren, Dianke Yu, Baitang Ning, Lei Guo
Dronedarone, an antiarrhythmic drug, has been marketed as an alternative to amiodarone. The use of dronedarone has been associated with severe liver injury; however, the mechanisms remain unclear. In this study, the possible mechanisms of dronedarone induced liver toxicity were characterized in HepG2 cells. Dronedarone decreased cells viability and induced apoptosis and DNA damage in a concentration- and time-dependent manner. Pretreatment of the HepG2 cells with apoptosis inhibitors (caspase-3, -8, and -9) or the necrosis inhibitor (Necrox-5), partially, but significantly, reduced the release of lactate dehydrogenase...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29368350/genotoxicity-of-fine-and-coarse-fraction-ambient-particulate-matter-in-immortalised-normal-tt1-and-cancer-derived-a549-alveolar-epithelial-cells
#13
Ian W H Jarvis, Zachary Enlo-Scott, Eszter Nagy, Ian S Mudway, Teresa D Tetley, Volker M Arlt, David H Phillips
Human exposure to airborne particulate matter (PM) is associated with adverse cardiopulmonary health effects, including lung cancer. Ambient PM represents a heterogeneous mixture of chemical classes including transition metals, polycyclic aromatic hydrocarbons (PAHs) and their derivatives such as nitro-PAHs, many of which are classified as putative carcinogens. As the primary site of human exposure to PM is the lungs, we investigated the response of two alveolar epithelial cell lines, the tumour-derived A549 and newly described TT1 cells, to fine and coarse PM collected from background and roadside locations...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29359355/influence-of-carnicor-venofer-and-sevelamer-on-the-levels-of-genotoxic-damage-in-end-stage-renal-disease-patients
#14
Susana Pastor, Elisabeth Coll, Lara Rodríguez-Ribera, Elitsa Stoyanova, Zuray F Corredor, Ricard Marcos
End-stage renal disease (ESRD) patients present high levels of phosphorus and calcium products in serum, which contribute to the development of vascular calcification and cardiovascular disease, and to low iron stores and carnitine deficiency. For these reasons, ESRD patients are generally supplemented with different medicines. Some of the most common treatments include the use of Carnicor, Venofer, and Sevelamer drugs. Carnicor is used as a source of L-carnitine, acting as antioxidant and neuroprotector. Venofer is used to reduce the deficit of iron...
May 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29668064/assessment-of-a-panel-of-cellular-biomarkers-and-the-kinetics-of-their-induction-in-comparing-genotoxic-modes-of-action-in-hepg2-cells
#15
Benjamin Kopp, Morgane Dario, Daniel Zalko, Marc Audebert
One major challenge for in vitro genotoxicology is the determination of the genotoxic mode of action of tested compounds. The quantification of the phosphorylation of the histones H3 (pH3) and H2AX (γH2AX) allows an efficient discrimination between aneugenic and clastogenic compounds. However, these two biomarkers do not permit to deduct the specific mechanisms involved in the action of clastogenic compounds. The aim of this study was to investigate other possible cellular biomarkers allowing differentiating clastogenic properties...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29668047/miniaturization-of-the-microsuspension-salmonella-microsome-assay-in-agar-microplates
#16
José Ricardo R M Zwarg, Daniel A Morales, Bianca S Maselli, Werner Brack, Gisela A Umbuzeiro
The Salmonella/microsome assay (Ames test) is the most widely used mutagenicity test for the evaluation of pure chemicals and environmental samples. There are several versions of protocols available in the literature, including those that reduce the amount of sample needed for testing with liquid and agar media. The microsuspension version of the Salmonella/microsome assay is more sensitive than the standard protocol. It is performed using 5-times concentrated bacteria and less sample and S9 mixture, but still uses conventional Petri dishes (90 × 15 mm)...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29668046/black-cohosh-extracts-and-powders-induce-micronuclei-a-biomarker-of-genetic-damage-in-human-cells
#17
Stephanie L Smith-Roe, Carol D Swartz, Kim G Shepard, Steven M Bryce, Stephen D Dertinger, Suramya Waidyanatha, Grace E Kissling, Scott S Auerbach, Kristine L Witt
Black cohosh extract (BCE) is a widely used dietary supplement marketed to women to alleviate symptoms of gynecological ailments, yet its toxicity has not been well characterized. The National Toxicology Program (NTP) previously reported significant increases in micronucleated erythrocytes in peripheral blood of female Wistar Han rats and B6C3F1/N mice administered 15-1,000 mg BCE/kg/day by gavage for 90 days. These animals also developed a dose-dependent nonregenerative macrocytic anemia characterized by clinical changes consistent with megaloblastic anemia...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29668043/folate-deficiency-increases-chromosomal-damage-and-mutations-in-hematopoietic-cells-in-the-transgenic-mutamouse-model
#18
Danielle P LeBlanc, Nathalie A Behan, Jason M O'Brien, Francesco Marchetti, Amanda J MacFarlane
Folate deficiency causes megaloblastic anemia and neural tube defects, and is also associated with some cancers. In vitro, folate deficiency increases mutation frequency and genome instability, as well as exacerbates the mutagenic potential of known environmental mutagens. Conversely, it remains unclear whether or not elevated folic acid (FA) intakes are beneficial or detrimental to the induction of DNA mutations and by proxy human health. We used the MutaMouse transgenic model to examine the in vivo effects of FA deficient, control, and supplemented diets on somatic DNA mutant frequency (MF) and genome instability in hematopoietic cells...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29656392/epigenetic-modifications-preserve-the-hyperaccumulator-noccaea-caerulescens-from-ni-geno-toxicity
#19
Mariolina Gullì, Laura Marchi, Rosaria Fragni, Annamaria Buschini, Giovanna Visioli
The Ni hyperaccumulator Noccaea caerulescens has adapted to live in a naturally stressed environment, evolving a complex pattern of traits to cope with adverse conditions. Evidence is accumulating regarding the important role of epigenetic modifications in regulating plant responses to stress. In this study, we present data from the natural "open-field" adaptation of the Ni hyperaccumulator N. caerulescens to serpentine soil and provide the first evidence of the involvement of epigenetic changes in response to the high Ni content present in plant leaves...
April 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29637621/assessment-of-sediment-mutagenicity-in-areas-under-the-influence-of-a-contaminated-site-undergoing-a-remediation-process
#20
Paula Hauber Gameiro, Naiara Costa Pereira, Jocelita Aparecida Vaz Rocha, Karen Alam Leal, Vera Maria Ferrão Vargas
Soil contamination enters aquatic ecosystems affecting sediment quality. The region studied is the Taquari River, Brazil, close to a site contaminated by wood preservatives, with a runoff route into the river. The first stage of the remediation process (In this article, the terms intervention and remediation have been used with slightly different meanings. We consider intervention to be the first phase of the remediation process, which aims to remove active sources) was an intervention to remove the main active sources...
April 10, 2018: Environmental and Molecular Mutagenesis
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