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Mutation Research

M Monserrat Pacheco-Martínez, Elsa Cervantes-Ríos, María Del Carmen García-Rodríguez, Rocío Ortiz-Muñiz
Severe malnutrition is a complex condition that increases susceptibility to infections. Thus, drugs are extensively used in malnutrition cases. In the present study, we assessed the mutagenic effects of combined trimethoprim and sulfamethoxazole (TMP-SMX) treatment in undernourished (UN) and well-nourished (WN) rats. Six-week-old UN and WN Han-Wistar rats were treated with TMP-SMX at a daily dose of 10 mg/kg/d TMP and 50 mg/kg/d SMX for 5 or 10 days. Blood was collected from the tail vein one day before (day -1) and 15, 30, and 45 days after TMP-SMX administration...
December 30, 2017: Mutation Research
Yan Du, Shanwei Luo, Lixia Yu, Tao Cui, Xia Chen, Jiangyan Yang, Xin Li, Wenjian Li, Jufang Wang, Libin Zhou
Heavy-ion beam irradiation is a powerful physical mutagen that has been used to create numerous mutant materials in plants. These materials are an essential resource for functional genomics research in the post-genome era. The advent of Next-Generation Sequencing (NGS) technology has promoted the study of functional genomics and molecular breeding. A wealth of information can be gathered from whole genome re-sequencing; however, understanding the molecular mutation profile at genome wide, as well as identifying causal genes for a given phenotype are big challenging issues for researchers...
December 9, 2017: Mutation Research
Pritha Bhattacharjee, Somnath Paul, Sandip Bhattacharjee, Ashok K Giri, Pritha Bhattacharjee
Arsenic, a non mutagenic carcinogen, poses a profound health risk upon prolonged exposure. The objective of the study was to analyze the post-translational modifications of the major histone H3 and the associated molecular crosstalk to identify the epigenetic signature of arsenic susceptibility. Herein, we identified significant upregulation of H3K79me1, in individuals with arsenic-induced skin lesion (WSL), and H3K79me1 was found to be regulated by the upstream methyltransferase DOT1L. Moreover, the downstream target molecule 53BP1, a tumor suppressor protein that has a docking preference for H3K79me1 at a site of a double-strand break (DSB), was downregulated, indicating greater DNA damage in the WSL group...
November 14, 2017: Mutation Research
Tejeshwori Salam, S Premila Devi, R H Duncan Lyngdoh
Alkylating agents and N-nitroso compounds are well-known mutagens and carcinogens which act by alkylating DNA at the nucleobase moieties. Criteria for mutagenicity through DNA alkylation include (a) absence of the Watson-Crick (N1-guanine and N3-thymine) protons, (b) rotation of the alkyl group away from the H-bonding zone, (c) configuration of the alkylated base pair close to the Watson-Crick type. This computational study brings together these three molecular criteria for the first time. Three methylated DNA bases-N7-methylguanine, O6-methylguanine and O4-methylthymine-are studied using computational chemical methods...
November 10, 2017: Mutation Research
Youichirou Matuo, Yoshinobu Izumi, Yoshiya Furusawa, Kikuo Shimizu
It has been established that irradiation with higher linear energy transfer (LET) increases lethality and mutagenicity more than that with lower LET. However, the characteristics specific to carbon ion beam have not yet been elucidated. Yeast cells were irradiated with carbon ions with an LET of 13 or 50keV/μm, and cell survival and mutation frequency were analyzed. The results, combined with our previous findings for ions with an LET of 107keV/μm, demonstrated that, in conjunction with an increase in LET, cell survival decreased, while mutation frequency increased...
November 7, 2017: Mutation Research
Avelyno H D'costa, Shyama S K, Praveen Kumar M K, Swizzle Furtado
The coast of Goa receives anthropogenic stress through its major rivers, which carry mining wastes, including iron and manganese ores from upstream mining sites, and petroleum hydrocarbons from shipping activities. These contaminants show seasonal variation in concentration and may be bioaccumulated by fauna inhabiting these waters. These fauna, including the bivalve molluscs, are particularly at risk due to these insults. In the present study, the use of the backwater clam, Meretrix casta (Chemnitz), as a bioindicator species was evaluated, comparing two sites (Vasco and Palolem) on the Goan coast...
January 2018: Mutation Research
Carlos Eduardo de Oliveira Costa Júnior, Leone Maltz Borges Silva, Thiago de Salazar E Fernandes, Alex Souza Moraes, Ademir Amaral, Edvane Borges
This study aimed at analyzing the frequency of micronuclei (MN) in exfoliated cells as well as the levels of Pb-210 in urine samples to evaluate the association between the smoking habit and toxic stress of transitional epithelial cells. The frequency of MN was scored from Giemsa-stained slides while exchange resin and beta counting techniques were employed to measure the concentrations of this radioisotope. Urine samples of smokers had levels of Pb-210 up to 158.65 mBq L-1. For nonsmokers, the median was below the detection limit (45 mBq L-1)...
January 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...
January 2018: Mutation Research
David P Lovell, Mick Fellows, Francesco Marchetti, Joan Christiansen, Azeddine Elhajouji, Kiyohiro Hashimoto, Sawako Kasamoto, Yan Li, Ozaki Masayasu, Martha M Moore, Maik Schuler, Robert Smith, Leon F Stankowski, Jin Tanaka, Jennifer Y Tanir, Veronique Thybaud, Freddy Van Goethem, James Whitwell
The recent revisions of the Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines emphasize the importance of historical negative controls both for data quality and interpretation. The goal of a HESI Genetic Toxicology Technical Committee (GTTC) workgroup was to collect data from participating laboratories and to conduct a statistical analysis to understand and publish the range of values that are normally seen in experienced laboratories using TK6 cells to conduct the in vitro micronucleus assay...
January 2018: Mutation Research
Maria Cristina S Barbosa, Camila de Souza Barbosa, Júlia T de Oliveira, Natália Chermont S Moreira, Natália Rezende de Miranda Martins, Gabrielle K Alves Gomes, Camila A Caldeira, Marília Ladeira Alves E Costa, Daniel Silqueira Martins Guimarães, Luciana Guimarães, Clebio S Nascimento, Fernando de Pilla Varotti, Gustavo Henrique Ribeiro Viana, Fabio Vieira Dos Santos
Theonella sp is an important source of biologically-active 3-alkylpyridine alkaloids (3-APAs) that has shown a wide variety of promising biological effects. In the present work, two new 3-APAs analogues were synthesized based on molecular modeling studies to act as potential antimalarial agents. These theoneladin C analogues, containing the thiocyanate group in their chemical structures, were synthesized and evaluated against Plasmodium falciparum (IC50 values ranging from 2.3 to 5.5μM). The structural and energetic analysis demonstrated a high chemical affinity of the two analogues for their target, the heme group...
January 2018: Mutation Research
Xihan Guo, Juan Ni, Xueqin Dai, Tao Zhou, Guofang Yang, Jinglun Xue, Xu Wang
Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin possessing numerous health-promoting effects. Chromosomal instability (CIN), usually results from defective spindle assembly checkpoint (SAC), is a major contributor to many diseases. While it's recently recognized that RSV exhibits a nonlinear dose response for disease prevention, whether it's the case for its role in CIN remains unknown. Here, we investigated the potential of a broad range of RSV concentrations (0.01-100μM) on CIN and the underlying mechanisms in human normal colon epithelial NCM460 cells...
January 2018: Mutation Research
Vehbi Atahan Toğay, Tuğba Semerci Sevimli, Murat Sevimli, Dilek Aşcı Çelik, Nurten Özçelik
Silibinin, the active component of Silybum marianum (L.), is a powerful antioxidant. Male rats with streptozotocin-induced diabetes were treated with silibinin. DNA damage was demonstrated by the comet assay in the control, diabetic, and treatment groups. DNA damage was increased in diabetic rats and decreased by silibinin treatment.
January 2018: Mutation Research
Kursat Gundogan, Hamiyet Donmez-Altuntas, Zuhal Hamurcu, Ismail Hakkı Akbudak, Murat Sungur, Nazmiye Bitgen, Gulden Baskol, Fahri Bayram
Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage...
January 2018: Mutation Research
Bani Bandana Ganguly, Shouvik Mandal
Following the 1984 Bhopal methyl isocyanate (MIC) gas disaster, genetic alterations were sporadically reported on small cohorts. However, the outcome of the multi-center cytogenetic screening conducted at that time remains unknown and no follow-up studies on the long-term effects of MIC exposure have been published. The present work examines genetic changes in the exposed population,with the aim of identifying any long-term effects of MIC. G-Banded metaphases were studied in lymphocytes of 130 individuals. Chromosomal aberrations (CA) were broadly grouped as abnormal cells (Abc), aberrations (Abn), and aberration/abnormal cell (Abn/Abc)...
December 2017: Mutation Research
Caroline Martins Sandanielo Marques, Emilene Arusievicz Nunes, Larissa Lago, Cibele Nicolaski Pedron, Tânia Maria Manieri, Roseli Hiromi Sato, Vani Xavier Oliveira, Giselle Cerchiaro
Glucose, in the presence of reactive oxygen species (ROS), acts as an as an oxidative agent and drives deleterious processes in Diabetes Mellitus. We have studied the mechanism and the toxicological effects of glucose-dependent glycoxidation reactions driven by copper and ROS, using a model peptide based on the exposed sequence of Human Serum Albumin (HSA) and containing a lysine residue susceptible to copper complexation. The main products of these reactions are Advanced Glycation End-products (AGEs). Carboxymethyl lysine and pyrraline condensed on the model peptide, generating a Modified Peptide (MP)...
December 2017: Mutation Research
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
Javier Alonso Ruiz-Guzmán, Pamela Gómez-Corrales, Ángel Cruz-Esquivel, José Luis Marrugo-Negrete
Pesticides offer benefits, like optimization of agricultural production and disease control; however, these toxic substances can contaminate the environment and pose risks to human health. The aim of this study was to assess pesticide exposure and frequency of cytogenetic damage in infant populations in agricultural areas of the department of Córdoba, Colombia. Urine and peripheral blood samples were taken from children living in the villages of La Ceibita (municipality of Cereté), Cabuya (municipality of San Carlos), Aguas Negras (municipality of Montería), Pelayito (municipality of San Pelayo), and the city of Monteria (control group)...
December 2017: Mutation Research
Mahmood Norishadkam, Soudeh Andishmand, Javad Zavar Reza, Mohammad Javad Zare Sakhvidi, Vida Rezae Hachesoo
Preterm birth infants are more susceptible to oxidative stress and aftermaths unwanted outcomes such as DNA damage due to hyperoxic stress. In this study, we compared the DNA strand breaks as one of the results of DNA oxidation in white blood cells, malondialdehyde (oxidative stress marker), catalase and superoxide dismutase activity, and total antioxidant capacity (markers of antioxidant defense) in a cord blood plasma of a group of preterm (n=25) and full term births (n=25). The primary DNA damage and plasma oxidative stress markers were significantly higher in a preterm group (p<0...
December 2017: Mutation Research
Javier Revollo, Yiying Wang, Page McKinzie, Azra Dad, Mason Pearce, Robert H Heflich, Vasily N Dobrovolsky
We used Sanger sequencing and next generation sequencing (NGS) for analysis of mutations in the endogenous X-linked Pig-a gene of clonally expanded L5178YTk(+/-) cells. The clones developed from single cells that were sorted on a flow cytometer based upon the expression pattern of the GPI-anchored marker, CD90, on their surface. CD90-deficient and CD90-proficient cells were sorted from untreated cultures and CD90-deficient cells were sorted from cultures treated with benzo[a]pyrene (B[a]P). Pig-a mutations were identified in all clones developed from CD90-deficient cells; no Pig-a mutations were found in clones of CD90-proficient cells...
December 2017: Mutation Research
Tatjana Čėsnienė, Violeta Kleizaitė, Skaistė Bondzinskaitė, Ričardas Taraškevičius, Donatas Žvingila, Raimondas Šiukšta, Vytautas Rančelis
Soil mutagens, particularly metals, may persist long after the source of pollution has been removed, representing a hazard to plants, animals, and humans in or near contaminated areas. Often, due to urban growth, previous land uses may be forgotten and hazards overlooked. We exposed Tradescantia clone #4430 plants to soil from two industrial areas (with different former uses) and two urban waste landfills in the city of Vilnius, all of which were long disused. Two modes of exposure were used: long-term exposure of growing plants in test soils for 0...
November 2017: Mutation Research
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