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Mutation Research

Ian E Burbulis, Margaret B Wierman, Matt Wolpert, Mark Haakenson, Maria-Beatriz Lopes, David Schiff, James Hicks, Justin Loe, Aakrosh Ratan, Michael J McConnell
Uneven replication creates artifacts during whole genome amplification (WGA) that confound molecular karyotype assignment in single cells. Here, we present an improved WGA recipe that increased coverage and detection of copy number variants (CNVs) in single cells. We examined serial resections of glioblastoma (GBM) tumor from the same patient and found low-abundance clones containing CNVs in clinically relevant loci that were not observable using bulk DNA sequencing. We discovered extensive genomic variability in this class of tumor and provide a practical approach for investigating somatic mosaicism...
July 8, 2018: Mutation Research
Shashi Bala, Neha Arora Chugh, Subhash Chand Bansal, Mohan Lal Garg, Ashwani Koul
The present study was aimed to explore the protective role of Aloe vera gel extract against hepatic and renal damage caused by X-ray exposure to mice. Male balb/c mice were divided into four groups: control, Aloe vera gel extract [AV] (50 mg/ kg b.w on alternate days for 30 days), X-ray (2 Gy) and AV + X-ray. X-ray irradiation enhanced the serum levels of liver function indices and chromosomal abnormalities in liver. Kidney function markers were found to be deranged and were accompanied by reduced glomerular filtration rate indicating renal dysfunction...
July 7, 2018: Mutation Research
Paul Fowler, Krista Meurer, Naveed Honarvar, David Kirkland
1,4-Naphthoquinone (1,4-NQ; CAS RN 130-15-4), a derivative of naphthalene, is a commonly used pre-cursor in industrial processes. Since the early 1980's 1,4-NQ has been tested in a number of genotoxicity assays, both in vitro and in vivo. There is strong evidence that 1,4-NQ does not induce gene mutations in bacteria or mammalian cells in vitro with predominantly negative Ames tests and negative Hprt and tk mutation studies. However, there is clear evidence of a clastogenic response in vitro from positive micronucleus, sister chromatid exchange and chromosome aberration assays...
October 2018: Mutation Research
Chie Furihata, Takeshi Toyoda, Kumiko Ogawa, Takayoshi Suzuki
It has long been unclear whether 1,4-dioxane (DO) is a genotoxic hepatocarcinogen (GTHC). Therefore, the present study aimed to evaluate rat GTHCs and non-genotoxic hepatocarcinogens (NGTHCs) via selected gene expression patterns in the liver, as determined by next generation sequencing-targeted mRNA sequencing (RNA-Seq) and principal component analysis (PCA). Previously, we selected 11 marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) to discriminate GTHCs and NGTHCs...
October 2018: Mutation Research
Guang Yang, Yukako Komaki, Yuko Ibuki
We recently reported that cigarette sidestream smoke (CSS) can delay nucleotide excision repair (NER), which was due to the inhibition of repair protein accumulation to DNA damage sites. However, the mechanisms how the protein recruitment was inhibited remains unclear. We hypothesized that aldehydes in CSS could be a candidate taking a role for the inhibition, and tested our hypothesis by removing aldehydes from CSS using cigarette-filters. The NER inhibition potency of CSS or filtered CSS (F-CSS) was compared using human keratinocyte cell line, HaCaT...
October 2018: Mutation Research
Ume-Kulsoom Shah, Jefferson de Oliveira Mallia, Neenu Singh, Katherine E Chapman, Shareen H Doak, Gareth J S Jenkins
The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing...
October 2018: Mutation Research
Hiroyuki Yanagisawa, Yoshiko Seki, Shingo Yogosawa, Shota Takumi, Hidesuke Shimizu, Machi Suka
The present study was designed to examine genotoxicity induced by 10-40 nm zinc oxide (ZnO) nanoparticles using the in vitro system. The frequency of micronuclei was significantly increased in a dose-dependent manner when cultured Chinese hamster lung (CHL/IU) cells were exposed to ZnO nanoparticles for 24, 48 and 72 h in the continuous treatment method. The maximal frequency of micronuclei was observed in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 125 μM. The frequency of micronuclei was profoundly enhanced when CHL/IU cells were exposed to ZnO nanoparticles in the presence vs...
October 2018: Mutation Research
Daniel Siquieroli Vilas Boas, Monique Matsuda, Odaly Toffoletto, Maria Lúcia Bueno Garcia, Paulo Hilário Nascimento Saldiva, Mônica Valéria Marquezini
Air pollution affects all major urban centers, particularly megacities with populations greater than 10 million people. Vehicular and industrial emissions are among the most important sources of air pollutants in these cities. Air pollution composition, dose, and time of exposure can cause differential effects on human health. We have evaluated the genotoxic effects of air pollution (PM2.5 and NO2 ) on São Paulo city workers. Fifty-seven male individuals, 28-66 years old, with occupational exposure to air pollution, participated in this study; all worked daily outdoor shifts in São Paulo...
October 2018: Mutation Research
Effat Behravan, Seyed Adel Moallem, Fatemeh Kalalinia, Mahnaz Ahmadimanesh, Peter Blain, Paul Jowsey, Shahriar Khateri, Mohammad Mahdi Forghanifard, Mahdi BalaliMood
Sulfur Mustard (SM) is the most widely used chemical weapon. It was used in World War 1 and in the more recent Iran-Iraq conflict. Genetic toxicity and DNA alkylation effects of SM in molecular and animal experiments are well documented. In this study, lymphocytic telomere lengths and serum levels of isoprostane F2α were measured using q-PCR and enzyme immunoassay-based methods in 40 Iranian veterans who had been exposed to SM between 1983-88 and 40 non-exposed healthy volunteers. The relative telomere length in SM-exposed individuals was found to be significantly shorter than the non-exposed individuals...
October 2018: Mutation Research
Francesco Marchetti, Marilyn J Aardema, Carol Beevers, Jan van Benthem, Roger Godschalk, Andrew Williams, Carole L Yauk, Robert Young, George R Douglas
The Organisation for Economic Co-operation and Development Test Guideline 488 (TG 488) provides recommendations for assessing germ cell and somatic cell mutagenicity using transgenic rodent (TGR) models. However, important data gaps exist for selecting an optimal approach for simultaneously evaluating mutagenicity in both cell types. It is uncertain whether analysis of germ cells from seminiferous tubules (hereafter, tubule germ cells) or caudal sperm within the recommended design for somatic tissues (i.e., 28 days of exposure plus three days of fixation time, 28 + 3d) has enough sensitivity to detect an effect as compared with the analysis of sperm within the recommended design for germ cells (i...
August 2018: Mutation Research
Mariana G Braz, Kátina M Souza, Lorena M C Lucio, Giulia C C Di Renzo, Luciana M Feliciano, João Paulo C Marcondes, C-Y Oliver Chen, José Reinaldo C Braz, Leandro G Braz
Operating room professionals are scarcely aware of their individual occupational exposure to waste anesthetic gases (WAGs). Medical residents spend several hours per day in operating rooms and consequently experience occupational exposure to WAGs. Considering that no studies have yet evaluated the potential toxicity in medical residents exposed to WAGs using the buccal micronucleus cytome (BMCyt) assay, this pioneering study aimed to compare the BMCyt assay markers, including DNA damage, cell proliferation, and cell death in the exfoliated buccal cells of surgery and anesthesiology residents occupationally exposed to WAGs...
August 2018: Mutation Research
Ilka Dayane Duarte de Sousa Coelho, Clovis José Cavalcanti Lapa Neto, Talita Giselly Dos Santos Souza, Meykson Alexandre da Silva, Cristiano Aparecido Chagas, Katharine Raquel Pereira Dos Santos, Valéria Wanderley Teixeira, Álvaro Aguiar Coelho Teixeira
Maternal alcoholism can induce serious injuries in embryonic and fetal development. The metabolism of alcohol increases the production of free radicals and acetaldehyde, molecules capable of reacting with DNA, impairing organogenesis. Melatonin is a powerful antioxidant that can act as a protective agent against DNA damage caused by genotoxic agents, such as ethanol. This study evaluated the protective effect of exogenous melatonin in rats and their offspring on the genotoxic response induced by chronic alcohol consumption during pregnancy...
August 2018: Mutation Research
Tandrima Mitra, Bimal Prasanna Mohanty, Sasmita Mohanty, Gopal Krishna Purohit, Basanta Kumar Das
The present study was undertaken to investigate the alterations in gene expression patterns and for mutation analysis of p53 in the riverine catfish Rita rita collected from polluted riverine habitat. The partial p53 gene sequence of Rita rita generated showed a high degree of similarities with the DNA binding domains of fishes, mice and human. Transcriptomic analysis, carried out by quantitative real-time Polymerase Chain Reaction (RT-qPCR), showed significant down-regulation of p53 in fishes collected from most of the polluted stretches...
August 2018: Mutation Research
Martina Richterova, Rudolf Stetina, Petr Jost, Hana Svobodova, Vit Rehacek, Jiri Kassa
Inter-strand crosslinks (ICL) in the DNA are regarded to be the main toxic lesions induced by sulphur mustard (SM). We have followed the induction of ICL in the DNA of different organs of Wistar rats and Balb/c or NMRI mice by the percutaneous application of SM using the modified (reverse) comet assay. Significant amounts of ICL were found in Balb/C lymphocytes, in bone marrow and liver cells after the dose of 80 mg/kg. A dose-dependent amount of ICL was induced in rats, with efficient induction in lymphocytes and spleen cells already after 5 mg SM/kg, indicating a higher susceptibility of rats to the DNA-damaging effect of SM compared with mice...
August 2018: Mutation Research
Tian-Jing Cai, Xue Lu, Xue-Lei Tian, Hua Zhao, Shuang Li, Jiang-Bin Feng, De-Qing Chen, Mei Tian, Qing-Jie Liu
Baseline nucleoplasmic bridges (NPB) vary widely in the general population from different regions in the same country or from different countries. The baseline NPB level in the normal Chinese population and the factors affecting the baseline and radiation-induced NPB levels have not been explored yet. The cytokinesis-block micronucleus cytome assay was conducted on the peripheral blood samples of 121 healthy individuals for the baseline NPB and 52 healthy individuals for the 2 Gy γ-ray-induced NPB level. The effects of age and gender on the baseline NPB and 2 Gy γ-ray-induced NPB level were evaluated...
August 2018: Mutation Research
Francesco Marchetti, Marilyn Aardema, Carol Beevers, Jan van Benthem, George R Douglas, Roger Godschalk, Carole L Yauk, Robert Young, Andrew Williams
The Organisation for Economic Co-operation and Development Test Guideline (TG) 488 for the transgenic rodent (TGR) mutation assay recommends two sampling times for assessing germ cell mutagenicity following the required 28-day exposure period: 28 + > 49 days for mouse sperm and 28 + >70 days for rat sperm from the cauda epididymis, or three days (i.e., 28 + 3d) for germ cells from seminiferous tubules (hereafter, tubule germ cells) plus caudal sperm for mouse and rat. Although the latter protocol is commonly used for mutagenicity testing in somatic tissues, it has several shortcomings for germ cell testing because it provides limited exposure of the proliferating phase of spermatogenesis when mutations are fixed in the transgene...
August 2018: Mutation Research
Huan Xu, Xiaolei Wang, Wei Wang
The carcinogenicity of arsenic has been confirmed in many studies, but its mechanism of action is still unclear. A lymphocyte component of the innate immune system, natural killer (NK) cells are responsible for killing cancer cells. Although inorganic arsenical species are the prevalent forms of arsenic in the environment, monomethylarsonous acid (MMA+3 ) is the major arsenical species found in immune-system cells, in this 30 d drinking-water-exposure study in mice. Therefore, the effect of MMA+3 on NK cells should be studied as a possible contributor to arsenic-induced toxicity at environmental exposure levels...
August 2018: Mutation Research
Tahereh Setayesh, Armen Nersesyan, Miroslav Mišík, Franziska Ferk, Sabine Langie, Vanessa M Andrade, Alexander Haslberger, Siegfried Knasmüller
Health authorities are alarmed worldwide about the increase of obesity and overweight in the last decades which lead to adverse health effects including inflammation, cancer, accelerated aging and infertility. We evaluated the state of knowledge concerning the impact of elevated body mass on genomic instability. Results of investigations with humans (39 studies) in which DNA damage was monitored in lymphocytes and sperm cells, are conflicting and probably as a consequence of heterogeneous study designs and confounding factors (e...
July 2018: Mutation Research
Pierre Brissot, Delphine G Bernard, Eolia Brissot, Olivier Loréal, Marie-Bérengère Troadec
Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds oxygen in the blood. It can be due to multiple causes, either acquired or genetic. Alterations of genes involved in iron metabolism may be responsible, usually at a young age, for rare forms of chronic and often severe congenital anemia. These diseases encompass a variety of sideroblastic anemias, characterized by the presence of ring sideroblasts in the bone marrow. Clinical expression of congenital sideroblastic anemia is either monosyndromic (restricted to hematological lineages) or polysyndromic (with systemic expression), depending on whether iron metabolism, and especially heme synthesis, is directly or indirectly affected...
July 2018: Mutation Research
Monique Nicole Helena Luijten, Jeannie Xue Ting Lee, Karen Carmelina Crasta
In recent years, the paradigm that genomic abnormalities in cancer cells arise through progressive accumulation of mutational events has been challenged by the discovery of single catastrophic events. One such phenomenon termed chromothripsis, involving massive chromosomal rearrangements arising all at once, has emerged as a major mutational game changer. The strong interest in this process stems from its widespread association with a range of cancer types and its potential as a mutational driver. In this review, we first describe chromothripsis detection and incidence in cancers...
July 2018: Mutation Research
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