-
Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients Mutagenesis (IF 3.379) Pub Date : 2020-12-26 Michal Kroupa; Sivaramakrishna Rachakonda; Veronika Vymetalkova; Kristyna Tomasova; Vaclav Liska; Sona Vodenkova; Andrea Cumova; Andrea Rossnerova; Ludmila Vodickova; Kari Hemminki; Pavel Soucek; Rajiv Kumar; Pavel Vodicka
Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and
-
Adaptation of the in vitro micronucleus assay for genotoxicity testing using 3D liver models supporting longer-term exposure durations. Mutagenesis (IF 3.379) Pub Date : 2020-08-11 Gillian E Conway,Ume-Kulsoom Shah,Samantha Llewellyn,Tereza Cervena,Stephen J Evans,Abdullah S Al Ali,Gareth J Jenkins,Martin J D Clift,Shareen H Doak
Following advancements in the field of genotoxicology, it has become widely accepted that 3D models are not only more physiologically relevant but also have the capacity to elucidate more complex biological processes that standard 2D monocultures are unable to. Whilst 3D liver models have been developed to evaluate the short-term genotoxicity of chemicals, the aim of this study was to develop a 3D
-
The genotoxic effects in the leukocytes of workers handling nanocomposite materials. Mutagenesis (IF 3.379) Pub Date : 2020-07-23 Bozena Novotna,Daniela Pelclova,Andrea Rossnerova,Vladimir Zdimal,Jakub Ondracek,Lucie Lischkova,Stepanka Vlckova,Zdenka Fenclova,Pavlina Klusackova,Tana Zavodna,Jan Topinka,Martin Komarc,Stepanka Dvorackova,Pavel Rossner
The extensive development of nanotechnologies and nanomaterials poses a number of questions to toxicologists about the potential health risks of exposure to nanoparticles (NP). In this study, we analysed DNA damage in the leukocytes of 20 workers who were long-term exposed (18 ± 10 years) to NP in their working environment. Blood samples were collected in September 2016, before and after a shift, to
-
DNA ligase I variants fail in the ligation of mutagenic repair intermediates with mismatches and oxidative DNA damage. Mutagenesis (IF 3.379) Pub Date : 2020-09-11 Qun Tang,Pradnya Kamble,Melike Çağlayan
DNA ligase I (LIG1) joins DNA strand breaks during DNA replication and repair transactions and contributes to genome integrity. The mutations (P529L, E566K, R641L and R771W) in LIG1 gene are described in patients with LIG1-deficiency syndrome that exhibit immunodeficiency. LIG1 senses 3’-DNA ends with a mismatch or oxidative DNA base inserted by a repair DNA polymerase. However, the ligation efficiency
-
Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer. Mutagenesis (IF 3.379) Pub Date : 2020-09-11 Kristina Daniunaite,Agne Sestokaite,Raimonda Kubiliute,Kristina Stuopelyte,Eeva Kettunen,Kirsti Husgafvel-Pursiainen,Sonata Jarmalaite
Cancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired
-
Synergic toxic effects of food contaminant mixtures in human cells. Mutagenesis (IF 3.379) Pub Date : 2020-08-18 Benjamin Kopp,Pascal Sanders,Imourana Alassane-Kpembi,Valérie Fessard,Daniel Zalko,Ludovic Le Hégarat,Marc Audebert
Humans are exposed to multiple exogenous substances, notably through food consumption. Many of these compounds are suspected to impact human health, and their combination could exacerbate their harmful effects. We previously observed in human cells that, among the six most prevalent food contaminant complex mixtures identified in the French diet, synergistic interactions between component appeared
-
Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells. Mutagenesis (IF 3.379) Pub Date : 2020-08-13 Ana Paula Braga Lima,Tamires Cunha Almeida,Tatiane Martins Barcelos Barros,Lorrana Cachuite Mendes Rocha,Camila Carriao Machado Garcia,Glenda Nicioli da Silva
The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of
-
Preliminary concerns with vaccine vectors. Mutagenesis (IF 3.379) Pub Date : 2020-08-12 Nevio Cimolai
Many aspects of vaccine development, efficacy and safety deserve the utmost of attention as unparalleled progress in this regard occurs at breakneck speed for COVID-19. Aspects of vaccine safety that proportionately lack discussion even publicly in the scientific arena, whether inadvertently or purposely, are the issues of mutagenesis or oncogenesis. As Ball suggests, anti-vaccine postures will arise
-
Melatonin supplementation over different time periods until ageing modulates genotoxic parameters in mice. Mutagenesis (IF 3.379) Pub Date : 2020-07-28 Adriani Paganini Damiani,Giulia Strapazzon,Thanielly Thais de Oliveira Sardinha,Paula Rohr,Goran Gajski,Ricardo Aurino de Pinho,Vanessa Moraes de Andrade
The ageing process is a multifactorial phenomenon, associated with decreased physiological and cellular functions and an increased propensity for various degenerative diseases. Studies on melatonin (N-acetyl-5-methoxytryptamine), a potent antioxidant, are gaining attention since melatonin production declines with advancing age. Hence, the aim of this study was to evaluate the effects of chronic melatonin
-
In vivo mutagenicity evaluation of the soil fumigant 1,3-dichloropropene Mutagenesis (IF 3.379) Pub Date : 2020-07-16 Melissa Badding; B Bhaskar Gollapudi; Sean Gehen; Zhongyu (June) Yan
1,3-Dichloropropene (1,3-D; CAS No. 542-75-6) is a soil fumigant used for the control of nematodes in agriculture. There is an extensive database on the genotoxicity of 1,3-D and many of the published studies are confounded by the presence of mutagenic stabilisers in the test substance. Mixed results were obtained in the in vitro assays, often due to the purity of the 1,3-D sample tested. In order
-
Pig-a gene mutation assay study design: critical assessment of 3- versus 28-day repeat-dose treatment schedules. Mutagenesis (IF 3.379) Pub Date : 2020-07-01 Azeddine Elhajouji,Tamsanqa Tafara Hove,Oliver O'Connell,Hansjoerg Martus,Stephen D Dertinger
The in vivo Pig-a assay is being used in safety studies to evaluate the potential of chemicals to induce somatic cell gene mutations. Ongoing work is aimed at developing an Organisation for Economic Cooperation and Development (OECD) test guideline to support routine use for regulatory purposes (OECD project number 4.93). Among the details that will need to be articulated in an eventual guideline are
-
Can a digital slide scanner and viewing technique assist the visual scoring for the cytokinesis-block micronucleus cytome assay? Mutagenesis (IF 3.379) Pub Date : 2020-05-08 Emma L Jaunay,Varinderpal S Dhillon,Susan J Semple,Bradley S Simpson,Permal Deo,Michael Fenech
The cytokinesis-block micronucleus cytome (CBMNcyt) assay is a comprehensive method to measure DNA damage, cytostasis and cytotoxicity caused by nutritional, radiation and chemical factors. A slide imaging technique has been identified as a new method to assist with the visual scoring of cells for the CBMNcyt assay. A NanoZoomer S60 Digital Pathology slide scanner was used to view WIL2-NS cells treated
-
Advanced glycation end-products accelerate telomere attrition and increase pro-inflammatory mediators in human WIL2-NS cells. Mutagenesis (IF 3.379) Pub Date : 2020-04-22 Permal Deo,Varinderpal S Dhillon,Wai Mun Lim,Emma L Jaunay,Leigh Donnellan,Brock Peake,Caitlin McCullough,Michael Fenech
This study investigated the effect of dietary sugars and advanced glycation end-products (AGE) on telomere dynamics in WIL2-NS cells. Dietary sugars [glucose (Glu) and fructose (Fru); 0.1 M each] were incubated with bovine serum albumin (BSA) (10 mg/ml) at 60 ± 1°C for 6 weeks to generate AGE-BSA. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed total AGE levels as 87.74 ± 4.46 nmol/mg
-
Potassium bromate as positive assay control for the Fpg-modified comet assay. Mutagenesis (IF 3.379) Pub Date : 2020-04-22 Peter Møller,Damian Muruzabal,Tamara Bakuradze,Elke Richling,Ezgi Eyluel Bankoglu,Helga Stopper,Sabine A S Langie,Amaya Azqueta,Annie Jensen,Francesca Scavone,Lisa Giovannelli,Maria Wojewódzka,Marcin Kruszewski,Vanessa Valdiglesias,Blanca Laffon,Carla Costa,Solange Costa,João Paulo Teixeira,Mirko Marino,Cristian Del Bo',Patrizia Riso,Sergey Shaposhnikov,Andrew Collins
The comet assay is a popular assay in biomonitoring studies. DNA strand breaks (or unspecific DNA lesions) are measured using the standard comet assay. Oxidative stress-generated DNA lesions can be measured by employing DNA repair enzymes to recognise oxidatively damaged DNA. Unfortunately, there has been a tendency to fail to report results from assay controls (or maybe even not to employ assay controls)
-
Validation of the 3D reconstructed human skin Comet assay, an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays Mutagenesis (IF 3.379) Pub Date : 2020-03-10 Stefan Pfuhler; Ralph Pirow; Thomas R Downs; Andrea Haase; Nicola Hewitt; Andreas Luch; Marion Merkel; Claudia Petrick; André Said; Monika Schäfer-Korting; Kerstin Reisinger
As part of the safety assessment process, all industrial sectors employ genotoxicity test batteries, starting with well-established in vitro assays. However, these batteries have limited predictive capacity for the in vivo situation, which may result in unnecessary follow-up in vivo testing or the loss of promising substances where animal tests are prohibited or not desired. To address this, a project
-
Mismatch repair systems might facilitate the chromosomal recombination induced by N-nitrosodimethylamine, but not by N-nitrosodiethylamine, in Drosophila. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Tomoe Negishi,Kenji Yamada,Keiko Miyamoto,Emiko Mori,Kentaro Taira,Asei Fujii,Yuki Goto,Sakae Arimoto-Kobayashi,Keinosuke Okamoto
Mismatch repair (MMR) systems play important roles in maintaining the high fidelity of genomic DNA. It is well documented that a lack of MMR increases the mutation rate, including base exchanges and small insertion/deletion loops; however, it is unknown whether MMR deficiency affects the frequency of chromosomal recombination in somatic cells. To investigate the effects of MMR on chromosomal recombination
-
The promise of toxicogenomics for genetic toxicology: past, present and future. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Rhiannon David
Toxicogenomics, the application of genomics to toxicology, was described as 'a new era' for toxicology. Standard toxicity tests typically involve a number of short-term bioassays that are costly, time consuming, require large numbers of animals and generally focus on a single end point. Toxicogenomics was heralded as a way to improve the efficiency of toxicity testing by assessing gene regulation across
-
Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Christopher Kirby,Ayesha Baig,Svetlana L Avlasevich,Dorothea K Torous,Shuchang Tian,Priyanka Singh,Jeffrey C Bemis,Lawrence J Saubermann,Stephen D Dertinger
Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant
-
Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Permal Deo,Caitlin L McCullough,Theodora Almond,Emma L Jaunay,Leigh Donnellan,Varinderpal S Dhillon,Michael Fenech
This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu-BSA) or with fructose (Fru-BSA). Liquid chromatography-mass spectrometry
-
Fructose consumption during pregnancy and lactation causes DNA damage and biochemical changes in female mice. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Marina Lummertz Magenis,Adriani Paganini Damiani,Pamela Souza de Marcos,Ellen de Pieri,Emanuel de Souza,Thais Ceresér Vilela,Vanessa Moraes de Andrade
The consumption of fructose during pregnancy can cause hyperglycaemia and may stimulate production of reactive oxygen species; however, there are only a few studies reporting whether fructose consumption during pregnancy causes DNA damage. Therefore, the aim of this study was to evaluate the effects of fructose consumption on genetic and biochemical parameters in Swiss mice treated during pregnancy
-
Effect of BRCA1 missense variants on gene reversion in DNA double-strand break repair mutants and cell cycle-arrested cells of Saccharomyces cerevisiae. Mutagenesis (IF 3.379) Pub Date : 2020-03-27 Samuele Lodovichi,Francesca Bellè,Tiziana Cervelli,Alessandra Lorenzoni,Luisa Maresca,Cristina Cozzani,Maria Adelaide Caligo,Alvaro Galli
Evaluation of the functional impact of germline BRCA1 variants that are likely to be associated to breast and ovarian cancer could help to investigate the mechanism of BRCA1 tumorigenesis. Expression of pathogenic BRCA1 missense variants increased homologous recombination (HR) and gene reversion (GR) in yeast. We thought to exploit yeast genetics to shed light on BRCA1-induced genome instability and
-
Genome-wide association study of germline copy number variations reveals an association with prostate cancer aggressiveness. Mutagenesis (IF 3.379) Pub Date : 2020-04-07 Stefanie Brezina,Moritz Feigl,Tanja Gumpenberger,Ricarda Staudinger,Andreas Baierl,Andrea Gsur
Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may
-
Telomere maintenance in interplay with DNA repair in pathogenesis and treatment of colorectal cancer. Mutagenesis (IF 3.379) Pub Date : 2020-02-21 Kristyna Tomasova,Michal Kroupa,Asta Forsti,Pavel Vodicka,Ludmila Vodickova
Colorectal cancer (CRC) continues to be one of the leading malignancies and causes of tumour-related deaths worldwide. Both impaired DNA repair mechanisms and disrupted telomere length homeostasis represent key culprits in CRC initiation, progression and prognosis. Mechanistically, altered DNA repair results in the accumulation of mutations in the genome and, ultimately, in genomic instability. DNA
-
A new 3D model for genotoxicity assessment: EpiSkin™ Micronucleus Assay. Mutagenesis (IF 3.379) Pub Date : 2020-02-18 Lizao Chen,Nan Li,Yanfeng Liu,Brigitte Faquet,Nathalie Alépée,Chunmei Ding,Joan Eilstein,Lingyan Zhong,Zhengang Peng,Jie Ma,Zhenzi Cai,Gladys Ouedraogo
The European Regulation on Cosmetics (no. 1223/2009) has prohibited the use of animals in safety testing since March 2009 for ingredients used in cosmetics. Irreversible events at the chromosome level (clastogenesis and aneugenesis) are commonly evaluated by scoring either micronuclei or chromosome aberrations using cell-based genotoxicity assays. Like most in vitro genotoxicity assays, the 2D in vitro
-
Implications of DNA damage and DNA repair on human diseases. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Bryant C Nelson,Miral Dizdaroglu
-
-
Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients. Mutagenesis (IF 3.379) Pub Date : 2020-01-10 Veronika Vymetalkova,Fabio Rosa,Simona Susova,Petra Bendova,Miroslav Levy,Tomas Buchler,Jan Kral,Linda Bartu,Ludmila Vodickova,David J Hughes,Pavel Soucek,Alessio Naccarati,Rajiv Kumar,Pavel Vodicka,Barbara Pardini
The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes
-
Genotoxicity assessment of four novel quinazoline-derived trypanocidal agents in the Drosophila wing somatic mutation and recombination test. Mutagenesis (IF 3.379) Pub Date : 2019-12-03 Luis Felipe Santos-Cruz,Bertha Guadalupe Ramírez-Cruz,Miguel García-Salomé,Zaira Yuriria Olvera-Romero,Francisco Hernández-Luis,Luis Barbo Hernández-Portilla,Ángel Durán-Díaz,Irma Elena Dueñas-García,Laura Castañeda-Partida,Elías Piedra-Ibarra,César Mendoza-Martínez,María Eugenia Heres-Pulido
Chagas disease, caused by the protozoan Trypanosoma cruzi, has increased in the world due to migration, travelling and climate change; at present, the principal problem is that common trypanocidal agents have resulted in toxic or inconvenient side effects. We tested for genotoxicity in the standard (ST) and high bioactivation (HB) crosses of Drosophila wing somatic mutation and recombination test,
-
Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review. Mutagenesis (IF 3.379) Pub Date : 2019-11-30 Antonio Francavilla,Szimonetta Turoczi,Sonia Tarallo,Pavel Vodicka,Barbara Pardini,Alessio Naccarati
The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest
-
miR-181a-2* expression is different amongst carcinomas from the colorectal serrated route. Mutagenesis (IF 3.379) Pub Date : 2019-11-30 Alexandra Kondelova,Begoña Alburquerque-González,Petra Vychytilova-Faltejskova,José García-Solano,Vladimir Prochazka,Zdenek Kala,Fernando Pérez,Ondrej Slaby,Pablo Conesa-Zamora
Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in
-
Requirements for DNA bubble structure for efficient cleavage by helix-two-turn-helix DNA glycosylases. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Kristina A Makasheva,Anton V Endutkin,Dmitry O Zharkov
Oxidative DNA lesions, constantly generated by both endogenous and environmentally induced reactive oxygen species, are removed via the base excision repair pathway. In bacteria, Fpg and Nei DNA glycosylases, belonging to the helix-two-turn-helix (H2TH) structural superfamily, remove oxidised purines and pyrimidines, respectively. Interestingly, the human H2TH family glycosylases, NEIL1, NEIL2 and
-
Mechanistic insight into the role of Poly(ADP-ribosyl)ation in DNA topology modulation and response to DNA damage. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Bakhyt T Matkarimov,Dmitry O Zharkov,Murat K Saparbaev
Genotoxic stress generates single- and double-strand DNA breaks either through direct damage by reactive oxygen species or as intermediates of DNA repair. Failure to detect and repair DNA strand breaks leads to deleterious consequences such as chromosomal aberrations, genomic instability and cell death. DNA strand breaks disrupt the superhelical state of cellular DNA, which further disturbs the chromatin
-
Urinary N7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans: temporal stability and association with smoking. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Caitlin C Jokipii Krueger,Guru Madugundu,Amanda Degner,Yesha Patel,Daniel O Stram,Timothy R Church,Natalia Tretyakova
1,3-Butadiene (BD) is a known human carcinogen found in cigarette smoke, automobile exhaust, and urban air. Workers occupationally exposed to BD in the workplace have an increased incidence of leukemia and lymphoma. BD undergoes cytochrome P450-mediated metabolic activation to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxybutane (DEB) and 1,2-dihydroxy-3,4-epoxybutane (EBD), which form covalent adducts with
-
DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives? Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Piotr Czarny,Katarzyna Bialek,Sylwia Ziolkowska,Justyna Strycharz,Tomasz Sliwinski
Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress
-
Altered DNA ligase activity in human disease. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Alan E Tomkinson,Tasmin Naila,Seema Khattri Bhandari
The joining of interruptions in the phosphodiester backbone of DNA is critical to maintain genome stability. These breaks, which are generated as part of normal DNA transactions, such as DNA replication, V(D)J recombination and meiotic recombination as well as directly by DNA damage or due to DNA damage removal, are ultimately sealed by one of three human DNA ligases. DNA ligases I, III and IV each
-
Chromatin and other obstacles to base excision repair: potential roles in carcinogenesis. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Paul J Caffrey,Sarah Delaney
DNA is comprised of chemically reactive nucleobases that exist under a constant barrage from damaging agents. Failure to repair chemical modifications to these nucleobases can result in mutations that can cause various diseases, including cancer. Fortunately, the base excision repair (BER) pathway can repair modified nucleobases and prevent these deleterious mutations. However, this pathway can be
-
Impact of hypoxia on DNA repair and genome integrity. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Alanna R Kaplan,Peter M Glazer
Hypoxia is a hallmark of the tumour microenvironment with profound effects on tumour biology, influencing cancer progression, the development of metastasis and patient outcome. Hypoxia also contributes to genomic instability and mutation frequency by inhibiting DNA repair pathways. This review summarises the diverse mechanisms by which hypoxia affects DNA repair, including suppression of homology-directed
-
Measurement of DNA damage with the comet assay in high-prevalence diseases: current status and future directions. Mutagenesis (IF 3.379) Pub Date : 2020-02-13 Peter Møller,Helga Stopper,Andrew R Collins
The comet assay is widely used in studies on genotoxicity testing, human biomonitoring and clinical studies. The simple version of the assay detects a mixture of DNA strand breaks and alkali-labile sites; these lesions are typically described as DNA strand breaks to distinguish them from oxidatively damaged DNA that are measured with the enzyme-modified comet assay. This review assesses the association
-
Genetic polymorphisms in inflammatory genes and pancreatic cancer risk: a two-phase study on more than 14 000 individuals. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Manuel Gentiluomo,Giulia Peduzzi,Ye Lu,Daniele Campa,Federico Canzian
There is overwhelming evidence that inflammation plays a key role in the pathogenesis of cancer and its progression. Inflammation is regulated through a complex network of genes and polymorphic variants in these genes have been found to be associated to risk of various human cancers, alone or in combination with environmental variables. Despite this, not much is known on the genetic variability of
-
Large deletions and untargeted substitutions induced by abasic site analog on leading versus lagging strand templates in human cells. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Tetsuya Suzuki,Yuri Katayama,Yasuo Komatsu,Hiroyuki Kamiya
The tetrahydrofuran-type abasic site analog (THF) induces large deletion mutations in human cells. To compare the large deletions induced by THF on leading and lagging strand templates, plasmid DNAs bearing the analog at a specific position outside the supF gene were introduced into human U2OS cells. The replicated DNAs recovered from the transfected cells were electroporated into an Escherichia coli
-
DNA polymerases in the risk and prognosis of colorectal and pancreatic cancers. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Roberto Silvestri,Stefano Landi
Human cancers arise from the alteration of genes involved in important pathways that mainly affect cell growth and proliferation. DNA replication and DNA damages recognition and repair are among these pathways and DNA polymerases that take part in these processes are frequently involved in cancer onset and progression. For example, damaging alterations within the proofreading domain of replicative
-
Extracranial arteriovenous malformations: from bedside to bench. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Congzhen Qiao,Gresham T Richter,Weijun Pan,Yunbo Jin,Xiaoxi Lin
Arteriovenous malformation (AVM) is defined as a fast-flow vascular anomaly that shunts blood from arteries directly to veins. This short circuit of blood flow contributes to progressive expansion of draining veins, resulting in ischaemia, tissue deformation and in some severe cases, congestive heart failure. Various medical interventions have been employed to treat AVM, however, management of which
-
Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Lindsay Reed,Ian W H Jarvis,David H Phillips,Volker M Arlt
The environmental carcinogen benzo[a]pyrene (BaP) is presumed to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. However, studies using the Hepatic Reductase Null (HRN) mouse model, in which cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes, is deleted specifically in hepatocytes, have shown that loss of hepatic POR-mediated CYP function
-
Genetic variants in taste-related genes and risk of pancreatic cancer. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Manuel Gentiluomo,Ye Lu,Federico Canzian,Daniele Campa
Pancreatic ductal adenocarcinoma is an aggressive and relatively rare cancer with a dismal 5-year survival rate and a clear genetic background. Genetic variants in taste receptors and taste-related genes have been associated with a variety of human traits and phenotypes among which several cancer types and pancreatic cancer risk factors. In this study, we analysed 2854 single-nucleotide polymorphisms
-
5-Hydroxymethylcytosine in cord blood and associations of DNA methylation with sex in newborns. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Olivia Solomon,Julia L Macisaac,Gwen Tindula,Michael S Kobor,Brenda Eskenazi,Nina Holland
DNA methylation has been widely studied for associations with exposures and health outcomes. Both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks that may function differently to impact gene expression; however, the most commonly used technology to assess methylation for population studies in blood use are the Illumina 450K and EPIC BeadChips, for which the traditional
-
Distinct pathways associated with chromosomal aberration frequency in a cohort exposed to genotoxic compounds compared to general population. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Yasmeen Niazi,Hauke Thomsen,Bozena Smolkova,Ludmila Vodickova,Soňa Vodenkova,Michal Kroupa,Veronika Vymetalkova,Alena Kazimirova,Magdalena Barancokova,Katarina Volkovova,Marta Staruchova,Per Hoffmann,Markus M Nöthen,Maria Dusinska,Ludovit Musak,Pavel Vodicka,Kari Hemminki,Asta Försti
Non-specific structural chromosomal aberrations (CAs) observed in peripheral blood lymphocytes of healthy individuals can be either chromosome-type aberrations (CSAs) or chromatid-type aberrations (CTAs) depending on the stage of cell division they are induced in and mechanism of formation. It is important to study the genetic basis of chromosomal instability as it is a marker of genotoxic exposure
-
KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 M Oliverius,D Flasarova,B Mohelnikova-Duchonova,M Ehrlichova,V Hlavac,M Kocik,O Strouhal,P Dvorak,I Ojima,P Soucek
The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel
-
XPD/ERCC2 mutations interfere in cellular responses to oxidative stress. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Leticia K Lerner,Natália C Moreno,Clarissa R R Rocha,Veridiana Munford,Valquíria Santos,Daniela T Soltys,Camila C M Garcia,Alain Sarasin,Carlos F M Menck
Nucleotide excision repair (NER) is a conserved, flexible mechanism responsible for the removal of bulky, helix-distorting DNA lesions, like ultraviolet damage or cisplatin adducts, but its role in the repair of lesions generated by oxidative stress is still not clear. The helicase XPD/ERCC2, one of the two helicases of the transcription complex IIH, together with XPB, participates both in NER and
-
Protein interactions in T7 DNA replisome inhibit the bypass of abasic site by DNA polymerase. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Zhenyu Zou,Tingting Liang,Zhongyan Xu,Jiayu Xie,Shuming Zhang,Weina Chen,Siqi Wan,Yihui Ling,Huidong Zhang
Abasic site as a common DNA lesion blocks DNA replication and is highly mutagenic. Protein interactions in T7 DNA replisome facilitate DNA replication and translesion DNA synthesis. However, bypass of an abasic site by T7 DNA replisome has never been investigated. In this work, we used T7 DNA replisome and T7 DNA polymerase alone as two models to study DNA replication on encountering an abasic site
-
Change in mutation frequency at a TP53 hotspot during culture of ENU-mutagenised human lymphoblastoid cells. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Masahiko Watanabe,Masae Toudou,Taeko Uchida,Misato Yoshikawa,Hiroaki Aso,Katsuya Suemaru
Mutations in oncogenes or tumour suppressor genes cause increases in cell growth capacity. In some cases, fully malignant cancer cells develop after additional mutations occur in initially mutated cells. In such instances, the risk of cancer would increase in response to growth of these initially mutated cells. To ascertain whether such a situation might occur in cultured cells, three independent cultures
-
The effect of polymorphisms in the promoter of the BIRC5 gene on the risk of oesophageal squamous cell carcinoma and patient's outcomes. Mutagenesis (IF 3.379) Pub Date : 2019-12-19 Na Wang,Yan Li,Rong-Miao Zhou,Sai-Jin Cui,Shi-Ru Cao,Xi Huang,Xiang-Ran Huo,Bao-En Shan
Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is an inhibitor of apoptosis proteins and plays a key role in apoptosis or programmed cell death. In the present study, we evaluated the effect of BIRC5 gene polymorphisms on the risk of developing oesophageal squamous cell carcinoma (ESCC) and patients' outcomes in a high-incidence population from northern China. A population-based case-control
-
Response of Sulfolobus solfataricus Dpo4 polymerase in vitro to a DNA G-quadruplex. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 Alexandra Berroyer,Gloria Alvarado,Erik D Larson
Repetitive DNA sequences support the formation of structures that can interrupt replication and repair, leading to breaks and mutagenesis. One particularly stable structure is G-quadruplex (G4) DNA, which is four-stranded and formed from tandemly repetitive guanine bases. When folded within a template, G4 interferes with DNA synthesis. Similar to non-duplex structures, DNA base lesions can also halt
-
DNA damage in human whole blood caused by radiopharmaceuticals evaluated by the comet assay. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 Heinz H Schmeiser,Karl-Rudolf Muehlbauer,Walter Mier,Ann-Christin Baranski,Oliver Neels,Antonia Dimitrakopoulou-Strauss,Peter Schmezer,Clemens Kratochwil,Frank Bruchertseifer,Alfred Morgenstern,Klaus Kopka
Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [225Ac]Ac-prostate-specific
-
ZnO nanoparticles-associated mitochondrial stress-induced apoptosis and G2/M arrest in HaCaT cells: a mechanistic approach. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 N V Srikanth Vallabani,Souvik Sengupta,Ritesh Kumar Shukla,Ashutosh Kumar
Zinc oxide nanoparticles (ZnO NPs) with their wide range of consumer applications in day-to-day life received great attention to evaluate their effects in humans. This study has been attempted to elucidate the DNA damage response mechanism in a dermal model exposed to ZnO NPs through Ataxia Telangiectasia Mutated (ATM)-mediated ChK1-dependent G2/M arrest. Further, viability parameters and mechanism
-
Quantitative analysis of mutagenicity and carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in F344 gpt delta transgenic rats. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 Min Gi,Masaki Fujioka,Yukari Totsuka,Michiharu Matsumoto,Kenichi Masumura,Anna Kakehashi,Takashi Yamaguchi,Shoji Fukushima,Hideki Wanibuchi
Quantitative analysis of the mutagenicity and carcinogenicity of the low doses of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the mutagenicity and carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 gpt delta transgenic rats were fed diets supplemented with 0, 0.1
-
The repeated cytogenetic analysis of subjects occupationally exposed to nanoparticles: a pilot study. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 Andrea Rossnerova,Daniela Pelclova,Vladimir Zdimal,Pavel Rossner,Fatima Elzeinova,Kristyna Vrbova,Jan Topinka,Jaroslav Schwarz,Jakub Ondracek,Martin Kostejn,Martin Komarc,Stepanka Vlckova,Zdenka Fenclova,Stepanka Dvorackova
The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched
-
Inclusion of an extended treatment with recovery improves the results for the human peripheral blood lymphocyte micronucleus assay. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 James Whitwell,Robert Smith,Teresa Chirom,Gary Watters,Victoria Hargreaves,Mel Lloyd,Sarah Phillips,Julie Clements
The in vitro micronucleus (IVMN) test was endorsed for regulatory genotoxicity testing with adoption of the Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 487 in 2010. This included two equally acceptable options for extended treatment in the absence of metabolic activation: a treatment for 1.5-2.0 cell cycles with harvest at the end of treatment (Option A) or treatment
-
Analysis of basal chromosome instability in patients with chronic lymphocytic leukaemia. Mutagenesis (IF 3.379) Pub Date : 2019-09-20 Micaela Palmitelli,Carmen Stanganelli,Flavia Stella,Andrea Krzywinski,Raimundo Bezares,Marcela González Cid,Irma Slavutsky
Genomic instability is a hallmark of cancer, contributing to tumour development and transformation, being chromosome instability (CIN) the most common form in human cancer. Chronic lymphocytic leukaemia (CLL) is the most frequent adult leukaemia in the Western world. In this study, we have evaluated basal CIN in untreated patients with CLL by measuring chromosome aberrations (CAs) and micronucleus
-
-