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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
Robyn A Lindley, Nathan E Hall
Cytosine and adenosine deamination events (DNA, RNA substrates) account for most codon-context Targeted Somatic Mutation (TSM) patterns observed in immunoglobulin (Ig) somatic hypermutation (SHM), and in cancer exomes following Ig-SHM-like responses. TSM refers to the process of somatic mutagenesis involving deamination events that results on a dominant type of mutation (e.g., C-to-T), and co-incident at a particular motif (e.g., WRC), and preferentially targeting the first, second or third nucleotide position within the mutated codon (e...
June 22, 2018: Mutation Research
Naoya Shikazono, Ken Akamatsu
Ionizing radiation causes various different types of DNA damage. If not repaired, DNA damage can have detrimental effects. Previous studies indicate that the spatial distribution of DNA lesions induced by ionizing radiation is highly relevant to the ensuing biological effects. Clustered DNA damage, consisting of DNA lesions in close proximity, has been studied in detail, and has enhanced mutagenic potential depending on the configuration of the lesions. However, it is not known whether clustered DNA damage affects the mutagenic potential of a sufficiently separated, isolated lesion...
May 26, 2018: Mutation Research
Anudishi Tyagi, Raja Pramanik, Sreenivas Vishnubhatla, Safdar Ali, Radhika Bakhshi, Anita Chopra, Archna Singh, Sameer Bakhshi
Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in acute myeloid leukaemia (AML). Consecutive 151 pediatric AML patients were prospectively enrolled from June 2013 to August 2016, for evaluating pattern of variations in mitochondrial D-loop region and to determine their association, if any, with expression of mitochondrial-encoded genes. For each patient, D-loop region was sequenced on baseline bone marrow, buccal swab and mother's blood sample. Real time PCR was used for relative gene expression of four mitochondrial DNA encoded genes viz...
May 24, 2018: Mutation Research
Min Zhang, Da Yang, Barry Gold
The enhanced incidence of colorectal cancer (CRC) in the U.S.A. has been linked to promutagens, such as heterocyclic aromatic amines, in the western diet that are produced by high temperature cooking of meat. However, a prior analysis of driver nonsense mutations in the Adenomatous Polyposis Coli (APC) gene, which is mutated in 75% of human CRC, indicated that the C·G → A·T transversions produced by this class of mutagens were not enriched but actually lower than what would be statistically anticipated...
May 1, 2018: Mutation Research
Maddaly Ravi, Aswathy S Lal, S Kauser Begum
Premature chromosome condensation (PCC) involves induction of near-chromosome-like morphology to interphase chromatin. Experimental induction of PCC was achieved by somatic cell hybridization (SCH), an approach which evolved into a chemical-induction process. PCC presents most probably the only way in which cytogenetic assessment of damages can be analyzed in special situations such as availability of limited numbers of sample cells and for cells which have lost their ability to divide. Initial experiments on PCC were reported in late 1960s and the technique has evolved into one with wide range of applications owing to its increased efficiency in detecting primary DNA damages...
July 2018: Mutation Research
Young-Shin Chung, Bumsoo Pak, Sehee Han, Jiyeon Lee, Jiyoung Kim, Seng-Min Back, Cho-Rong Park, Su-Hwan Kim, Jong-Kwon Lee
The mutagenic potencies of 1,3-propane sultone (PS), N-propyl-N-nitrosourea (PNU), and mitomycin C (MMC) were investigated in three independent laboratories in Korea using the Pig-a assay in vivo. Sprague-Dawley rats were treated with vehicle or test substance on three consecutive days. Blood samples were collected for measuring Pig-a mutant phenotypes (CD59-deficient erythrocytes, RBCCD59- ; CD59-deficient reticulocytes, RETCD59- ) on days -1, 15, and 29 after the first treatment. In some studies, blood was collected for determining DNA damage (comet assay) on day 3 and measuring micronucleated reticulocytes (MN-RET) on day 4...
July 2018: Mutation Research
Neha Paraswani, Maikho Thoh, Hari N Bhilwade, Anu Ghosh
The radiation-induced adaptive response (RI-AR) is a non-targeted effect which is outside the scope of the classical Linear-No-Threshold (LNT) dose-response paradigm. However, the mechanisms of the RI-AR are not well understood. We have studied the RI-AR in quiescent human peripheral blood mononuclear cells (PBMCs). PBMCs in G0 phase were 'primed' with a low dose (100 mGy gamma radiation) and then, after an 'adaptive window' of 4 h, 'challenged' with a high dose (2 Gy). A small (5.7%) increase in viability and a decrease in DNA strand breaks were seen in primed cells, compared to non-primed cells...
July 2018: Mutation Research
Deepa Rajesh, Sharath Balakrishna, S M Azeem Mohiyuddin, T N Suresh, A V Moideen Kutty
Glutathione S Transferases (GST) are anti-oxidant enzymes involved in detoxification of cellular and exogenous carcinogens and oxidative products of reactive oxygen species. Genetic polymorphisms can attenuate the detoxification capacity of GST and consequently increase the susceptibility to carcinogenesis. There are eight classes of GST enzymes of which pi subtype is the predominant form expressed in the oral mucosa. c.341C > T single nucleotide polymorphism (rs1138272) in GSTP1 gene, is a functional variation that reduces the enzymatic activity of GST pi...
July 2018: Mutation Research
Bernd-Wolfgang Igl, Stephen D Dertinger, Vasily N Dobrovolsky, Marian Raschke, Andreas Sutter, Richardus Vonk
The in vivo Pig-a gene mutation assay serves to evaluate the genotoxic potential of chemicals. In the rat blood-based assay, the lack of CD59 on the surface of erythrocytes is quantified via fluorophore-labeled antibodies in conjunction with flow cytometric analysis to determine the frequency of Pig-a mutant phenotype cells. The assay has achieved regulatory relevance as it is suggested as an in vivo follow-up test for Ames mutagens in the recent ICH M7 [25] step 4 document. However, very little work exists regarding suitable statistical approaches for analyzing Pig-a data...
July 2018: Mutation Research
R J Webster, A Williams, F Marchetti, C L Yauk
Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches...
July 2018: Mutation Research
Sara Sario, Amélia M Silva, Isabel Gaivão
Titanium dioxide nanoparticles (TiO2 NP) are used in the food, drug, and cosmetics industries and evaluation of their human and environmental toxicity is required. We have tested the toxicity of TiO2 NP (anatase) with respect to developmental effects and DNA damage in Drosophila melanogaster strain Ok, using the eye-spot Somatic Mutation and Recombination Test (SMART) and the comet assay (neuroblasts). For the survival assay, TiO2 NP were supplied to adult flies for 72 h and no adverse effects were seen. TiO2 NP were supplied chronically for the prolificacy, SMART, and comet assays...
July 2018: Mutation Research
Serazhutdin Abdullaev, Gulchachak Minkabirova, Ekaterina Karmanova, Vadim Bruskov, Azhub Gaziev
An antidiabetic drug metformin has anticarcinogenic and geroprotective effects and has been used in combination with radiation cancer therapy. The present work is devoted to the study of the effect of metformin on survival in mice, the frequency of micronuclei in mouse bone marrow cells and excretion of cell-free nuclear and mitochondrial DNA in the urine of X-ray-exposed rats. The survival rate and the frequency of micronuclei in mice and excretion of DNA into rat urine were determined after administration of the drug before and after irradiation of animals...
July 2018: Mutation Research
Constanza Cortés, Ricard Marcos
The presence of water disinfection byproducts (DBPs) in tap water, resulting from disinfection processes involving chlorination or chloramination, increases the mutagenicity of the water and may pose adverse health effects. The topic was reviewed by DeMarini and coworkers in 2007. Here, we review research on the genotoxicity of DBPs published since that time. Studies, primarily using the Salmonella mutagenicity assay, have continued to show that chlorination or chloramination of source waters results in finished, tap, or swimming pool/spa water that is more mutagenic than the original source water...
July 2018: Mutation Research
Kyungjae Myung
No abstract text is available yet for this article.
May 2018: Mutation Research
Qi Zheng
The mutation frequency, also known as the mutant frequency, is an unnormalized quantity, and its normalized counterpart is the mutation rate. Due to historical reasons, the mutation frequency has been a predominant yardstick of microbial mutability in the field of mutator identification. While the mean mutation frequency is infamously erratic, replacing it with the median mutation frequency is not an effective remedy. By encouraging investigators to substitute mutation rates for mutation frequencies in microbial research, this paper directs attention to substantial open problems such as false positive control and massive nonmutant cell death...
May 2018: Mutation Research
Rola Barcham, Nicolas Orsini, Eric Andres, Alexander Hundt, Anne-Pascale Luzy
We investigated the commercially available Episkin LM™ reconstructed epidermis test system as a potential 3D model for human genotoxicity assessment by cytokinesis-block micronucleus assay to mitigate limitations of the currently accepted micronucleus test. We established appropriate culture conditions for cytokinesis-block micronucleus assay in maximizing the frequency of binucleated cells by choice of culture medium and calibration of the system exposure to the cytokinesis inhibitor Cytochalasin B, without affecting the basal frequency of micronuclei in the model...
May 2018: Mutation Research
Phouthone Keohavong, Qing Lan, Weimin Gao
Lung cancer mortality in Xuan Wei County (XWC) is among the highest in China. Lung cancer in XWC is associated with exposure, in poorly vented homes, to coal smoke containing high levels of polycyclic aromatic hydrocarbons (PAHs). We have previously investigated mutations in the p53 tumor suppressor gene and the K-ras oncogene in lung carcinomas and in sputum samples from individuals exposed to smoky coal emissions in XWC. This paper summarizes the results concerning p53 and K-ras mutations from these studies, in relation to mutations found in lung cancer patients not exposed to smoky coal emissions...
May 2018: Mutation Research
Javier R Revollo, Azra Dad, Lea P McDaniel, Mason G Pearce, Vasily N Dobrovolsky
Genetic toxicology assays estimate mutation frequencies by phenotypically screening for the activation or inactivation of endogenous or exogenous reporter genes. These reporters can only detect mutations in narrow areas of the genome and their use is often restricted to certain in vitro and in vivo models. Here, we show that Interclonal Genetic Variation (ICGV) can directly identify mutations genome-wide by comparing sequencing data of single-cell clones derived from the same source or organism. Upon ethyl methanesulfonate (EMS) exposure, ICGV detected greater levels of mutation in a dose- and time-dependent manner in E...
May 2018: Mutation Research
Mohammad Sabbir Siddiqui, Maxime Francois, Jane Hecker, Jeffrey Faunt, Michael F Fenech, Wayne R Leifert
An early cellular response to DNA double-strand breaks is the phosphorylation of histone H2AX to form γH2AX. Although increased levels of γH2AX have been reported in neuronal nuclei of Alzheimer's disease (AD) patients, γH2AX responses in the lymphocytes of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In this study, the endogenous γH2AX level was measured, using laser scanning cytometry (LSC) and visual scoring, in lymphocyte nuclei from MCI (n = 18), or AD (n = 20) patients and healthy controls (n = 40)...
May 2018: Mutation Research
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