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Mutation Research

Neil J Sargentini, Nicholas P Gularte, Deborah A Hudman
A set of 3907 single-gene knockout (Keio collection) strains of Escherichia coli K-12 was examined for strains with increased susceptibility to killing by X- or UV-radiation. After screening with a high-throughput resazurin-based assay and determining radiation survival with triplicate clonogenic assays, we identified 76 strains (and associated deleted genes) showing statistically-significant increased radiation sensitivity compared to a control strain. To determine gene novelty, we constructed a reference database comprised of genes found in nine similar studies including ours...
October 3, 2016: Mutation Research
Nandana Das, Allan Giri, Sayan Chakraborty, Pritha Bhattacharjee
Long term consumption of arsenic contaminated water causes a number of dermatological and non-dermatological health problems and cancer. In a Genome Wide Association Study (GWAS) on Bangladesh population, a significant association of asingle nucleotide polymorphism (SNP) in the C10orf32 region (rs 9527; G>A) with urinary metabolites and arsenic induced skin lesions was reported. This study aims to evaluate the association of the C10orf32 G to A polymorphism (rs9527), concerned with As3MT read-through transcription, with the development of arsenic induced skin lesions in the arsenic exposed individuals of West Bengal, India...
October 2016: Mutation Research
Deepu Oommen, Nicholas J F Dodd, Dennis Yiannakis, Rana Moyeed, Awadhesh N Jha
Auranofin, an organogold compound classified as an anti-rheumatic agent is under phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is also implicated in modulating resistance to chemotherapeutics...
October 2016: Mutation Research
Paul Fowler, Andrew Homan, Derek Atkins, James Whitwell, Melvyn Lloyd, Roberta Bradford
A range of fibrous materials, including several types of asbestos and carbon fibres with nano scale diameters that had reported positive genotoxicity data (predominantly clastogenicity), were tested in the in vitro micronucleus test (OECD 487) in GLP-compliant studies in Chinese Hamster Ovary cells. Out of eight materials tested, only one (crocidolite, an asbestos fibre) gave a positive response either in the presence or absence of metabolic activation (S9) and at short (3h) or extended (24h) exposure times (p≤0...
October 2016: Mutation Research
Mohsen Cheki, Alireza Shirazi, Aziz Mahmoudzadeh, Javad Tavakkoly Bazzaz, Seyed Jalal Hosseinimehr
Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50μM for 2h and irradiated with 6MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow cytometry...
October 2016: Mutation Research
Clara Bocchi, Cristina Bazzini, Federica Fontana, Giancarlo Pinto, Anna Martino, Francesca Cassoni
Urban particulate matter (PM) is an environmental public health concern as it has been classified by the IARC as carcinogenic to humans (group 1) and it's well known that pollutants are more associated with the finest fractions of PM. In this study we characterize urban aerosol in Bologna, county town of Emilia-Romagna in the north of Italy, collecting PM2.5, PM1 and semi-volatile organic compounds using polyurethane foam. Samples were collected in three different seasons (winter, summer and autumn) and were extracted with acetone...
October 2016: Mutation Research
E Lorge, M M Moore, J Clements, M O'Donovan, M D Fellows, M Honma, A Kohara, S Galloway, M J Armstrong, V Thybaud, B Gollapudi, M J Aardema, J Y Tanir
Good cell culture practice and characterization of the cell lines used are of critical importance in in vitro genotoxicity testing. The objective of this initiative was to make continuously available stocks of the characterized isolates of the most frequently used mammalian cell lines in genotoxicity testing anywhere in the world ('IVGT' cell lines). This project was organized under the auspices of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing...
October 2016: Mutation Research
Inna B Korzeneva, Svetlana V Kostuyk, Elizaveta S Ershova, Elena N Skorodumova, Veronika F Zhuravleva, Galina V Pankratova, Irina V Volkova, Elena V Stepanova, Lev N Porokhovnik, Natalia N Veiko
A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body...
September 2016: Mutation Research
Kátina M Souza, Leandro G Braz, Flávia R Nogueira, Marajane B Souza, Lahis F Bincoleto, Aline G Aun, José E Corrente, Lídia R Carvalho, José Reinaldo C Braz, Mariana G Braz
Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide - N2O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group...
September 2016: Mutation Research
Tetsuya Suzuki, Petr Grúz, Masamitsu Honma, Noritaka Adachi, Takehiko Nohmi
Translesion DNA synthesis (TLS) is a cellular defense mechanism against genotoxins. Defects or mutations in specialized DNA polymerases (Pols) involved in TLS are believed to result in hypersensitivity to various genotoxic stresses. Here, DNA polymerase ζ (Pol ζ)-deficient (KO: knockout) and Pol ζ catalytically dead (CD) human cells were established and their sensitivity towards cytotoxic activities of various genotoxins was examined. The CD cells were engineered by altering the DNA sequence encoding two amino acids essential for the catalytic activity of Pol ζ, i...
September 2016: Mutation Research
Lei Zhao, Ying Gao, Dong Mi, Yeqing Sun
To identify the potential biomarkers associated with space flight, a combined algorithm, which integrates the feature selection techniques, was used to deal with the microarray datasets of Caenorhabditis elegans obtained in the Shenzhou-8 mission. Compared with the ground control treatment, a total of 86 differentially expressed (DE) genes in responses to space synthetic environment or space radiation environment were identified by two filter methods. And then the top 30 ranking genes were selected by the random forest algorithm...
September 2016: Mutation Research
Vivian Francília Silva Kahl, Juliana da Silva, Fernanda Rabaioli da Silva
Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood...
September 2016: Mutation Research
Agnieszka Halas, Michal Krawczyk, Ewa Sledziewska-Gojska
Homologous recombination is crucial in both the maintenance of genome stability and the generation of genetic diversity. Recently, multiple aspects of the recombination machinery functioning at arrested DNA replication forks have been established, yet the roles of diverse modifications of PCNA, the key platform organizing the replication complex, in intrachromosomal recombination have not been comprehensively elucidated. Here, we report how PCNA SUMOylation and/or polyubiquitination affects recombination between direct repeats in S...
September 2016: Mutation Research
Ting Wang, Wei Xu, Chenguang Deng, Shaoxin Xu, Fanghua Li, Yuejin Wu, Lijun Wu, Po Bian
Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot...
September 2016: Mutation Research
Mari Tagel, Kairi Tavita, Rita Hõrak, Maia Kivisaar, Heili Ilves
Formation of microcolonies (papillae) permits easy visual screening of mutational events occurring in single colonies of bacteria. In this study, we have established a novel papillation assay employable in a wide range of pseudomonads including Pseudomonas aeruginosa and Pseudomonas putida for monitoring mutation frequency in distinct colonies. With the aid of this assay, we conducted a genome-wide search for the factors affecting mutation frequency in P. putida. Screening ∼27,000 transposon mutants for increased mutation frequency allowed us to identify 34 repeatedly targeted genes...
August 2016: Mutation Research
Petra Lakatos, Csaba Hegedűs, Nerea Salazar Ayestarán, Ángeles Juarranz, Katalin E Kövér, Éva Szabó, László Virág
A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2...
August 2016: Mutation Research
Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Yohei Fujishima, Mitsuo Oshimura, Mitsuaki A Yoshida
Chromosome missegregation can lead to a change in chromosome number known as aneuploidy. Although aneuploidy is a known hallmark of cancer cells, the various mechanisms by which altered gene and/or DNA copy number facilitate tumorigenesis remain unclear. To understand the effect of aneuploidy occurring in non-tumorigenic human breast epithelial cells, we generated clones harboring artificial aneuploidy using microcell-mediated chromosome transfer. Our results demonstrate that clones with artificial aneuploidy of chromosome 8 or chromosome 22 both show inhibited proliferation and genomic instability...
August 2016: Mutation Research
Furqan Sami, Ronald K Gary, Yayin Fang, Sudha Sharma
RecQ helicases are a highly conserved family of ATP-dependent DNA-unwinding enzymes with key roles in DNA replication and repair in all kingdoms of life. The RECQ1 gene encodes the most abundant RecQ homolog in humans. We engineered full-length RECQ1 harboring point mutations in the zinc-binding motif (amino acids 419-480) within the conserved RecQ-specific-C-terminal (RQC) domain known to be critical for diverse biochemical and cellular functions of RecQ helicases. Wild-type RECQ1 contains a zinc ion. Substitution of three of the four conserved cysteine residues that coordinate zinc severely impaired the ATPase and DNA unwinding activities but retained DNA binding and single strand DNA annealing activities...
August 2016: Mutation Research
Jian Zhang, Ziyi Liu, Aoshuang Chang, Jie Fang, Yuqin Men, Yong Tian, Xiaomei Ouyang, Denise Yan, Aizhen Zhang, Xiaoyang Sun, Jie Tang, Xuezhong Liu, Jian Zuo, Jiangang Gao
Prestin is critical to OHC somatic motility and hearing sensitivity in mammals. Several mutations of the human SLC26A5 gene have been associated with deafness. However, whether the IVS2-2A>G mutation in the human SLC26A5 gene causes deafness remains controversial. In this study, we created a mouse model in which the IVS2-2A>G mutation was introduced into the mouse Slc26a5 gene by gene targeting. The homozygous Slc26a5 mutant mice were viable and fertile and displayed normal hearing sensitivity by ABR threshold analysis...
August 2016: Mutation Research
Wei Xu, Ting Wang, Shaoxin Xu, Fanghua Li, Chenguang Deng, Lijun Wu, Yuejin Wu, Po Bian
Plant stress responses at the epigenetic level are expected to allow more permanent changes of gene expression and potentially long-term adaptation. While it has been reported that plants subjected to adverse environments initiate various stress responses in their neighboring plants, little is known regarding epigenetic responses to external stresses mediated by plant-plant communication. In this study, we show that DNA repetitive elements of Arabidopsis thaliana, whose expression is inhibited epigenetically by transcriptional gene silencing (TGS) mechanism, are activated by UV-C irradiation through airborne plant-plant and plant-plant-plant communications, accompanied by DNA demethylation at CHH sites...
August 2016: Mutation Research
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