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Mutagenesis

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https://www.readbyqxmd.com/read/29346610/novel-mutations-in-the-lipase-h-gene-lead-to-secretion-defects-of-liph-in-chinese-patients-with-autosomal-recessive-woolly-hair-hypotrichosis-arwh-ht
#1
Xiao-Dan Chang, Ya-Juan Gu, Shan Dai, Xue-Rong Chen, Chun-Lei Zhang, Hong-Shan Zhao, Qing-Hua Song
Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a rare hereditary hair disease characterized by tightly curled hair at birth which can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5 are responsible for autosomal recessive woolly hair with or without hypotrichosis (ARWH/HT). To conduct clinical and genetic investigations in four patients from three unrelated Chinese Han families with ARWH/HT, we performed mutation screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH: c...
January 13, 2018: Mutagenesis
https://www.readbyqxmd.com/read/29329446/standardisation-of-the-in-vitro-comet-assay-influence-of-lysis-time-and-lysis-solution-composition-on-the-detection-of-dna-damage-induced-by-x-rays
#2
José M Enciso, Kristine B Gutzkow, Gunnar Brunborg, Ann-Karin Olsen, Adela López de Cerain, Amaya Azqueta
The alkaline comet assay, in vivo and in vitro, is currently used in several areas of research and in regulatory genotoxicity testing. Several efforts have been made in order to decrease the inter-experimental and inter-laboratory variability and increase the reliability of the assay. In this regard, lysis conditions are considered as one of the critical variables and need to be further studied. Here, we tested different times of lysis (from no lysis to 1 week) and two different lysis solutions in human lymphoblast (TK6) cells unexposed or exposed to X-rays...
January 10, 2018: Mutagenesis
https://www.readbyqxmd.com/read/29325088/the-comet-assay-ready-for-30-more-years
#3
Peter Møller
During the last 30 years, the comet assay has become widely used for the measurement of DNA damage and repair in cells and tissues. A landmark achievement was reached in 2016 when the Organization for Economic Co-operation and Development adopted a comet assay guideline for in vivo testing of DNA strand breaks in animals. However, the comet assay has much more to offer than being an assay for testing DNA strand breaks in animal organs. The use of repair enzymes increases the range of DNA lesions that can be detected with the assay...
January 6, 2018: Mutagenesis
https://www.readbyqxmd.com/read/29301028/influence-of-dispersion-medium-on-nanomaterial-induced-pulmonary-inflammation-and-dna-strand-breaks-investigation-of-carbon-black-carbon-nanotubes-and-three-titanium-dioxide-nanoparticles
#4
Niels Hadrup, Stefan Bengtson, Nicklas R Jacobsen, Petra Jackson, Marek Nocun, Anne T Saber, Keld A Jensen, Håkan Wallin, Ulla Vogel
Intratracheal instillation serves as a model for inhalation exposure. However, for this, materials are dispersed in appropriate media that may influence toxicity. We tested whether different intratracheal instillation dispersion media influence the pulmonary toxicity of different nanomaterials. Rodents were intratracheally instilled with 162 µg/mouse/1620 µg/rat carbon black (CB), 67 µg/mouse titanium dioxide nanoparticles (TiO2) or 54 µg/mouse carbon nanotubes (CNT). The dispersion media were as follows: water (CB, TiO2); 2% serum in water (CB, CNT, TiO2); 0...
December 30, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29294093/reduction-of-dna-damage-in-peripheral-lymphocytes-of-obese-patients-after-bariatric-surgery-mediated-weight-loss
#5
Ezgi Eyluel Bankoglu, Florian Seyfried, Charlotte Arnold, Alexander Soliman, Christian Jurowich, Christoph Thomas Germer, Christoph Otto, Helga Stopper
Obesity is associated with several detrimental health consequences, among them an increased risk for development of cancer, and an overall elevated mortality. Multiple factors like hyperinsulinemia, chronic microinflammation and oxidative stress may be involved. The comet assay has been proven to be very sensitive for detection of DNA damage and has been used to explore the relationship between overweight/obesity and DNA damage, but results are controversial. Very few investigations have been performed to correlate weight loss of obese individuals and possible reduction of DNA damage and these studies have not provided clear results...
December 23, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29244183/dna-damage-and-epigenetic-alteration-in-soybean-farmers-exposed-to-complex-mixture-of-pesticides
#6
Danieli Benedetti, Barbara Lopes Alderete, Claudia Telles de Souza, Johnny Ferraz Dias, Liana Niekraszewicz, Mónica Cappetta, Wilner Martínez-López, Juliana Da Silva
Exposure to pesticides can trigger genotoxic and mutagenic processes through different pathways. However, epidemiological studies are scarce, and further work is needed to find biomarkers sensitive to the health of exposed populations. Considering that there are few evaluations of soybean farmers, the aim of this study was to assess the effects of human exposure to complex mixtures of pesticides. The alkaline comet assay modified with restriction enzyme (hOGG1: human 8-oxoguanine DNA glycosylase) was used to detect oxidised guanine, and compared with the buccal micronucleus cytome assay, global methylation, haematological parameters, biochemical analyses (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl-transferase and butyrylcholinesterase), and particle-induced X-ray emission (PIXE) for the analysis of inorganic elements...
December 13, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29240951/using-the-comet-assay-and-lysis-conditions-to-characterize-dna-lesions-from-the-acrylamide-metabolite-glycidamide
#7
Siri Helland Hansen, Agnieszka J Pawlowicz, Leif Kronberg, Kristine Bjerve Gützkow, Ann-Karin Olsen, Gunnar Brunborg
The alkaline comet assay and a cell-free system were used to characterise DNA lesions induced by treatment with glycidamide (GA), a metabolite of the food contaminant acrylamide. DNA lesions induced by GA were sensitively detected when the formamidopyrimidine-DNA-glycosylase (Fpg) enzyme was included in the comet assay. We used LC-MS to characterise modified bases from GA-treated naked DNA with and without subsequent Fpg treatment. N7-GA-Guanine and N3-GA-Adenine aglycons were detected in the supernatant showing some depurination of adducted bases; treatment of naked DNA with Fpg revealed no further increase in the adduct yield nor occurrence of other adducted nucleobases...
December 12, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29237049/the-comet-assay-in-human-biomonitoring-cryopreservation-of-whole-blood-and-comparison-with-isolated-mononuclear-cells
#8
Gudrun Koppen, Sofie De Prins, An Jacobs, Vera Nelen, Greet Schoeters, Sabine A S Langie
The comet assay is often applied in human biomonitoring. Most of the time the assay is performed with isolated peripheral blood mononuclear cells (PBMC). However, using whole blood instead of isolated cells reduces processing time, and only 20 µl is sufficient for analysis. In this study, a cryopreservation protocol for human whole blood for application in the comet assay was optimised by removing excess plasma before adding freezing medium. Cryopreservation of whole blood samples (n = 30) did not increase the detected level of strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites...
December 9, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29237063/spectrum-of-pig-a-mutations-in-t-lymphocytes-of-rats-treated-with-procarbazine
#9
Javier Revollo, Javed A Bhalli, Cameron Tebbe, Jessica Noteboom, Demetria Thomas, Page McKinzie, Nicholas Felton, Mason G Pearce, Vasily N Dobrovolsky
Procarbazine is a primary component of antineoplastic combination chemotherapy often used for the treatment of Hodgkin's lymphoma. It is believed that cytostatic and cytotoxic properties of procarbazine are mediated via its interaction with genomic DNA. Procarbazine is a carcinogen in animal models; it is classified as Group 2A compound by IARC. Also it is known as an in vitro and in vivo mutagen and genotoxicant. However, the molecular mechanism by which procarbazine induces mutations is not thoroughly understood and the spectrum of procarbazine-induced in vivo mutations is described insufficiently...
December 8, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29186507/pyridylhydroxybutyl-and-pyridyloxobutyl-dna-phosphate-adduct-formation-in-rats-treated-chronically-with-enantiomers-of-the-tobacco-specific-nitrosamine-metabolite-4-methylnitrosamino-1-3-pyridyl-1-butanol
#10
Bin Ma, Adam T Zarth, Erik S Carlson, Peter W Villalta, Irina Stepanov, Stephen S Hecht
The tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolically converted to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in a reaction which is both stereoselective and reversible. NNAL is also a lung carcinogen, with both (R)-NNAL and (S)-NNAL inducing a high incidence of lung tumours in rats. Both NNAL and NNK undergo metabolic activation to intermediates which react with DNA to form pyridylhydroxybutyl and pyridyloxobutyl DNA adducts, respectively. DNA adduct formation by NNAL and NNK is an important step in their mechanisms of carcinogenesis...
November 27, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29165592/folate-deficiency-induces-mitotic-aberrations-and-chromosomal-instability-by-compromising-the-spindle-assembly-checkpoint-in-cultured-human-colon-cells
#11
Xihan Guo, Juan Ni, Yuqian Zhu, Tao Zhou, Xiaoling Ma, Jinglun Xue, Xu Wang
Folates comprise the essential B9 vitamin that act as cofactors and cosubstrates in one-carbon metabolism for both biosynthesis and methylation of DNA and RNA. Folate deficiency (FD) has been shown to induce chromosomal instability (CIN), yet the underlying mechanisms are poorly understood. Here, we used human NCM460 colon mucosal cells as a model to investigate the effect of FD on spindle assembly checkpoint (SAC), a cell-cycle regulatory pathway preventing CIN during mitosis. Cells were maintained in medium containing 1...
November 19, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29077953/the-comet-assay-applied-to-cells-of-the-eye
#12
Amaya Azqueta, Elisa Rundén-Pran, Elisabeth Elje, Bjørn Nicolaissen, Kristiane Haug Berg, Ingrida Smeringaiova, Katerina Jirsova, Andrew R Collins
The human eye is relatively unexplored as a source of cells for investigating DNA damage. There have been some clinical studies, using cells from surgically removed tissues, and altered DNA bases as well as strand breaks have been measured using the comet assay. Tissues examined include corneal epithelium and endothelium, lens capsule, iris and retinal pigment epithelium. For the purpose of biomonitoring for exposure to potential mutagens in the environment, the eye-relatively unprotected as it is compared with the skin-would be a valuable object for study; non-invasive techniques exist to collect lachrymal duct cells from tears, or cells from the ocular surface by impression cytology, and these methods should be further developed and validated...
October 25, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29048576/monitoring-characteristics-and-genotoxic-effects-of-engineered-nanoparticle-protein-corona
#13
Violet Aileen Senapati, Krupa Kansara, Rishi Shanker, Alok Dhawan, Ashutosh Kumar
Engineered nanoparticles (ENPs) possess different physical and chemical properties compared to their bulk counterparts. These unique properties have found application in various products in the area of therapeutics, consumer goods, environmental remediation, optical and electronic fields. This has also increased the likelihood of their release into the environment thereby affecting human health and ecosystem. ENPs, when in contact with the biological system have various physical and chemical interactions with cellular macromolecules including proteins...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29048575/microrna-binding-site-polymorphisms-in-genes-involved-in-colorectal-cancer-etiopathogenesis-and-their-impact-on-disease-prognosis
#14
Michaela Schneiderova, Alessio Naccarati, Barbara Pardini, Fabio Rosa, Cornelia Di Gaetano, Katerina Jiraskova, Alena Opattova, Miroslav Levy, Karel Veskrna, Veronika Veskrnova, Tomas Buchler, Stefano Landi, Pavel Vodicka, Veronika Vymetalkova
According to the Vogelstein's model of colorectal carcinogenesis, genetic variations in highly penetrant genes may be involved in the colorectal cancer (CRC) pathogenesis. Similarly, aberrant function and/or altered expression of microRNAs (miRNAs) often occur in CRC. In this context, polymorphisms in miRNA-binding sites (miRSNPs) may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and increased susceptibility to common diseases. To explore this phenomenon, we have mined the 3' untranslated regions (3'UTRs) of genes known to be frequently mutated in CRC to search for miRSNPs and tested their association with CRC risk and clinical outcome...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29045752/genome-size-and-sensitivity-to-dna-damage-by-x-rays-plant-comets-tell-the-story
#15
John Einset, Andrew R Collins
Among several factors affecting radiation sensitivity, genome size has received limited attention during the last 50 years since research at Brookhaven National Laboratory (USA) and other locations demonstrated substantial differences in radiation sensitivities, e.g. between tree species with large (e.g. conifers such as pines) versus small (e.g. dicots such as oaks) genome sizes. Taking advantage of the wide range of genome sizes among species, we investigated radiation sensitivity which we define in this study as DNA damage (break frequency) measured with the alkaline comet assay in isolated nuclei exposed to X-rays...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29040706/inhibition-of-survivin-expression-after-using-oxaliplatin-and-vinflunine-to-induce-cytogenetic-damage-in-vitro-in-lymphocytes-from-colon-cancer-patients-and-healthy-individuals
#16
Amal A A Alotaibi, Mojgan Najafzadeh, Justin D Davies, Adolf Baumgartner, Diana Anderson
Chemotherapy drugs usually inflict a lethal dose to tumour cells with the consequence that these cells are being killed by cell death. However, each round of chemotherapy also causes damage to normal somatic cells. The DNA cross-linking agent oxaliplatin (OXP), which causes DNA double-strand breaks, and vinflunine (VFN), which disrupts the mitotic spindle, are two of these chemotherapy drugs which were evaluated in vitro using peripheral lymphocytes from colorectal cancer patients and healthy individuals to determine any differential response...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29045708/association-between-polycyclic-aromatic-hydrocarbon-exposure-and-peripheral-blood-mononuclear-cell-dna-damage-in-human-volunteers-during-fire-extinction-exercises
#17
Maria Helena Guerra Andersen, Anne Thoustrup Saber, Per Axel Clausen, Julie Elbæk Pedersen, Mille Løhr, Ali Kermanizadeh, Steffen Loft, Niels Ebbehøj, Åse Marie Hansen, Peter Bøgh Pedersen, Ismo Kalevi Koponen, Eva-Carina Nørskov, Peter Møller, Ulla Vogel
This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP)...
October 13, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29036349/seasonal-variations-as-predictive-factors-of-the-comet-assay-parameters-a-retrospective-study
#18
Marko Geric, Goran Gajski, Višnja Orešcanin, Vera Garaj-Vrhovac
Since there are several predicting factors associated with the comet assay parameters, we have decided to assess the impact of seasonal variations on the comet assay results. A total of 162 volunteers were retrospectively studied, based on the date when blood donations were made. The groups (winter, spring, summer and autumn) were matched in terms of age, gender, smoking status, body mass index and medical diagnostic exposure in order to minimise the impact of other possible predictors. Means and medians of the comet assay parameters were higher when blood was sampled in the warmer period of the year, the values of parameters being the highest during summer...
September 19, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28992346/searching-for-assay-controls-for-the-fpg-and-hogg1-modified-comet-assay
#19
Peter Møller, Kim Jantzen, Mille Løhr, Maria Helena Andersen, Ditte Marie Jensen, Martin Roursgaard, Pernille Høgh Danielsen, Annie Jensen, Steffen Loft
The formamidopyrimidine DNA glycosylase (Fpg) and human 8-oxoguanine DNA glycosylase (hOGG1)-modified comet assays have been widely used in human biomonitoring studies. The purpose of this article is to assess differences in reported levels of Fpg- and hOGG1-sensitive sites in leukocytes and suggest suitable assay controls for the measurement of oxidatively damaged DNA. An assessment of the literature showed a large variation in the reported levels of Fpg-sensitive sites (range 0.05-1.31 lesions/106 bp). The levels of Fpg-sensitive sites are lower in studies where Fpg has been obtained from commercial suppliers or unknown sources as compared to Fpg from one particular non-commercial source (χ2 = 7...
September 15, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28992336/molecular-and-cytogenetic-effects-of-thai-royal-jelly-modulation-through-c-myc-h-tert-nrf2-ho-1-bcl2-bax-and-cyclins-in-human-lymphocytes-in-vitro
#20
Wantha Jenkhetkan, Sumon Thitiorul, Chalerm Jansom, Treetip Ratanavalachai
Royal jelly (RJ) is widely used as a food supplement for anti-aging and beauty. However, its use has been linked to asthma and hemorrhagic colitis. Since its mechanisms of toxicity have not been fully identified, we conducted an investigation to elucidate its molecular and cytogenetic effects. Using human lymphocytes in vitro, treatments with RJ (0.0005-5 mg/ml) for 3 h did not induce sister chromatid exchanges until 5 mg/ml was used. Treatments for 24 h showed a dose-dependent reduction in BCL2/BAX, c-MYC/BAX and HO-1/BAX ratios...
September 15, 2017: Mutagenesis
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