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Mutagenesis

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https://www.readbyqxmd.com/read/28096451/quantitative-relationships-between-lacz-mutant-frequency-and-dna-adduct-frequency-in-muta%C3%A2-mouse-tissues-and-cultured-cells-exposed-to-3-nitrobenzanthrone
#1
Paul A White, George R Douglas, David H Phillips, Volker M Arlt
The frequency of stable DNA adducts in a target tissue can be used to assess biologically effective dose; however, the utility of the metric in a risk assessment context depends on the likelihood that the DNA damage will be manifested as mutation. Previously, we employed the Muta™Mouse system to examine the induction of lacZ mutants and DNA adducts following exposure to the well-studied mutagenic carcinogen 3-nitrobenzanthrone (3-NBA). In this follow-up work, we examined the empirical relationships between total adduct frequency and mutant frequency (MF) in tissues and cultured cells following acute 3-NBA exposure...
January 16, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28096450/analysis-of-genome-instability-biomarkers-in-children-with-non-syndromic-orofacial-clefts
#2
Luíza Araújo da Costa Xavier, João Felipe Bezerra, Adriana Augusto de Rezende, Raffael Azevedo de Carvalho Oliveira, Rodrigo Juliani Siqueira Dalmolin, Viviane Souza do Amaral
The non-syndromic cleft lip and/or palate (NSCL/P) is a common birth defect caused by a combination of genetic and environmental factors. The possible role of genome instability on NSCL/P patient needs more investigation, since DNA metabolism is an essential cellular function to keep cells with normal genotypes and gene expression patterns according to tissue specificities, which is critical during embryo development because it requires sensitive regulation of cell proliferation, apoptosis and differentiation...
January 16, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28057708/development-of-an-in-vitro-pig-a-gene-mutation-assay-in-human-cells
#3
Benjamin J Rees, Matthew Tate, Anthony M Lynch, Catherine A Thornton, Gareth J Jenkins, Richard M Walmsley, George E Johnson
Mutagens can be carcinogens, and traditionally, they have been identified in vitro using the Salmonella 'Ames' reverse mutation assay. However, prokaryotic DNA packaging, replication and repair systems are mechanistically very different to those in the humans we inevitably seek to protect. Therefore, for many years, mammalian cell line genotoxicity assays that can detect eukaryotic mutagens as well as clastogens and aneugens have been used. The apparent lack of specificity in these largely rodent systems, due partly to their mutant p53 status, has contributed to the use of animal studies to resolve data conflicts...
January 4, 2017: Mutagenesis
https://www.readbyqxmd.com/read/27993944/effects-of-airborne-toxicants-on-pulmonary-function-and-mitochondrial-dna-damage-in-rodent-lungs
#4
William L Rumsey, Brian Bolognese, Alicia B Davis, Pearl L Flamberg, Joseph P Foley, Steven R Katchur, Charles J Kotzer, Ruth R Osborn, Patricia L Podolin
Inhalation of airborne toxicants such as cigarette smoke and ozone is a shared health risk among the world's populations. The use of toxic herbicides like paraquat (PQ) is restricted by many countries, yet in the developing world PQ has demonstrable ill effects. The present study examined changes in pulmonary function, mitochondrial DNA (mtDNA) integrity and markers of DNA repair induced by acute or repeated exposure of PQ to rats. Similar to cigarette smoke and ozone, PQ promotes oxidative stress, and the impact of PQ on mtDNA was compared with that obtained with these agents...
December 18, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27932515/genotoxic-effect-of-iron-overload-and-disease-complications-in-transfused-%C3%AE-thalassaemic-patients
#5
Elisa Ferro, Giuseppa Visalli, Maria Angela La Rosa, Basilia Piraino, Rosa Civa, Gaetano Randazzo Papa, Angela Di Pietro
In previously reported studies, we observed significantly high genotoxicity biomarkers in regularly transfused thalassaemic patients, thus, in this study, we better investigated the genotoxic effect of iron overload and of thalassaemia complications, including their drug treatments. The assessment was performed in 64 regularly transfused thalassaemic patients using cytokinesis-block micronucleus and comet assays. All patients were splenectomised and undergoing iron chelation therapy. To reduce hypoxia-induced oxidative damage, the patients with haemoglobin levels <9...
December 8, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27831478/radio-adaptive-response-in-peripheral-blood-lymphocytes-of-individuals-residing-in-high-level-natural-radiation-areas-of-kerala-in-the-southwest-coast-of-india
#6
E N Ramachandran, C V Karuppasamy, V Anil Kumar, D C Soren, P R Vivek Kumar, P K M Koya, G Jaikrishan, Birajalaxmi Das
The present study investigates whether the chronic low-dose radiation exposure induces an in vivo radio-adaptive response in individuals from high-level natural radiation areas (HLNRA) of the Kerala coast. Peripheral blood samples from 54 adult male individuals aged between 26 and 65 years were collected for the study with written informed consent. Each of the whole blood sample was divided into three, one was sham irradiated, second and third was exposed to challenging doses of 1.0 and 2.0 Gy gamma radiation, respectively...
November 9, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27816931/underlying-role-of-mitochondrial-mutagenesis-in-the-pathogenesis-of-a-disease-and-current-approaches-for-translational-research
#7
Maria Paraskevaidi, Pierre L Martin-Hirsch, Maria Kyrgiou, Francis L Martin
Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease...
November 5, 2016: Mutagenesis
https://www.readbyqxmd.com/read/28011751/editors-note
#8
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/28011750/epigenetic-effects-of-carbon-nanotubes-in-human-monocytic-cells
#9
Deniz Öner, Matthieu Moisse, Manosij Ghosh, Radu C Duca, Katrien Poels, Katrien Luyts, Eveline Putzeys, Stevan M Cokic, Kirsten Van Landuyt, Jeroen Vanoirbeek, Diether Lambrechts, Lode Godderis, Peter H M Hoet
Carbon nanotubes (CNTs) are fibrous carbon-based nanomaterials with a potential to cause carcinogenesis in humans. Alterations in DNA methylation on cytosine-phosphate-guanidine (CpG) sites are potential markers of exposure-induced carcinogenesis. This study examined cytotoxicity, genotoxicity and DNA methylation alterations on human monocytic cells (THP-1) after incubation with single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). Higher cytotoxicity and genotoxicity were observed after incubation with SWCNTs than incubation with MWCNTs...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/28011749/integrated-biological-responses-and-tissue-specific-expression-of-p53-and-ras-genes-in-marine-mussels-following-exposure-to-benzo-%C3%AE-pyrene-and-c60-fullerenes-either-alone-or-in-combination
#10
Yanan Di, Yann Aminot, Declan C Schroeder, James W Readman, Awadhesh N Jha
We used the marine bivalve (Mytilus galloprovincialis) to assess a range of biological or biomarker responses following exposure to a model-engineered nanoparticle, C60 fullerene, either alone or in combination with a model polycyclic aromatic hydrocarbon, benzo(α)pyrene [B(α)P]. An integrated biomarker approach was used that included: (i) determination of 'clearance rates' (a physiological indicator at individual level), (ii) histopathological alterations (at tissue level), (iii) DNA strand breaks using the comet assay (at cellular level) and (iv) transcriptional alterations of p53 (anti-oncogene) and ras (oncogene) determined by real-time quantitative polymerase chain reaction (at the molecular/genetic level)...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/28011748/genotoxicity-and-gene-expression-analyses-of-liver-and-lung-tissues-of-mice-treated-with-titanium-dioxide-nanoparticles
#11
Yan Li, Jian Yan, Wei Ding, Ying Chen, Lindsay M Pack, Tao Chen
Titanium dioxide nanoparticles (TiO2 NPs) are used in paints, plastics, papers, inks, foods, toothpaste, pharmaceuticals and cosmetics. However, TiO2 NPs cause inflammation, pulmonary damage, fibrosis and lung tumours in animals and are possibly carcinogenic to humans. Although there are a large number of studies on the toxicities of TiO2 NPs, the data are inconclusive and the mechanisms underlying the toxicity are not clear. In this study, we used the Comet assay to evaluate genotoxicity and whole-genome microarray technology to analyse gene expression pattern in vivo to explore the possible mechanisms for toxicity and genotoxicity of TiO2 NPs...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/28011747/nanogenotoxicology-present-and-the-future
#12
Shareen H Doak, Maria Dusinska
This Mutagenesis special issue is on the topic of nanogenotoxicology. It unites a collection of reports that provide insight into: (i) the properties of engineered nanomaterials (ENMs) that contribute to genotoxicity, (ii) the genotoxic mechanisms associated with DNA damage observed in both in vitro and in vivo tests and (iii) the future test systems that will provide more accurate prediction of ENM genotoxicity to support regulatory hazard assessment frameworks. The contributions within therefore provide collective oversight of our current understanding, coupled to future perspectives aimed at overcoming technical hurdles and describing novel analytical methods to further advance the field...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27864332/weak-silica-nanomaterial-induced-genotoxicity-can-be-explained-by-indirect-dna-damage-as-shown-by-the-ogg1-modified-comet-assay-and-genomic-analysis
#13
Stefan Pfuhler, Thomas R Downs, Ashley J Allemang, Yuching Shan, Meredith E Crosby
In a previous study, 15-nm silica nanoparticles (NPs) caused small increases in DNA damage in liver as measured in the in vivo comet and micronucleus assays after intravenous administration to rats at their maximum tolerated dose, a worst-case exposure scenario. Histopathological examination supported a particle-induced, tissue damage-mediated inflammatory response. This study used a targeted approach to provide insight into the mode of action (MoA) by examining transcriptional regulation of genes in liver in a time and dose-dependent manner at 1, 2, 4, 8 and 24 h after intravenous administration of 15-nm silica NPs...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27838631/in-vitro-genotoxicity-testing-of-four-reference-metal-nanomaterials-titanium-dioxide-zinc-oxide-cerium-oxide-and-silver-towards-reliable-hazard-assessment
#14
Naouale El Yamani, Andrew R Collins, Elise Rundén-Pran, Lise Marie Fjellsbø, Sergey Shaposhnikov, Shanbeh Zielonddiny, Maria Dusinska
There is serious concern about the potential harmful effects of certain nanomaterials (NMs), on account of their ability to penetrate cell membranes and the increased reactivity that results from their increased surface area compared with bulk chemicals. To assess the safety of NMs, reliable tests are needed. We have investigated the possible genotoxicity of four representative NMs, derived from titanium dioxide, zinc oxide, cerium oxide and silver, in two human cell lines, A549 alveolar epithelial cells and lymphoblastoid TK6 cells...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27834732/oxidant-generation-dna-damage-and-cytotoxicity-by-a-panel-of-engineered-nanomaterials-in-three-different-human-epithelial-cell-lines
#15
Waluree Thongkam, Kirsten Gerloff, Damien van Berlo, Catrin Albrecht, Roel P F Schins
Due to the steeply increased use of nanomaterials (NMs) for commercial and industrial applications, toxicological assessment of their potential harmful effects is urgently needed. In this study, we compared the DNA-damaging properties and concurrent cytotoxicity of a panel of 10 engineered NMs in three different cell lines in relation to their intrinsic oxidant generating properties. The human epithelial cell lines A549, HK-2 and HepG2 were chosen to represent relevant target organs for NMs in the lung, kidney and liver...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27815329/critical-review-of-the-current-and-future-challenges-associated-with-advanced-in-vitro-systems-towards-the-study-of-nanoparticle-secondary-genotoxicity
#16
REVIEW
Stephen J Evans, Martin J D Clift, Neenu Singh, Jefferson de Oliveira Mallia, Michael Burgum, John W Wills, Thomas S Wilkinson, Gareth J S Jenkins, Shareen H Doak
With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27803034/comparison-of-the-dna-damage-response-in-beas-2b-and-a549-cells-exposed-to-titanium-dioxide-nanoparticles
#17
M Biola-Clier, D Beal, S Caillat, S Libert, L Armand, N Herlin-Boime, S Sauvaigo, T Douki, M Carriere
For some decades production of titanium dioxide nanoparticle (TiO2-NP) has been increasing at a considerable rate; concerns as to the toxicity of these particles upon inhalation have been raised. Indeed, TiO2-NPs have been shown to induce significant genotoxicity and to adversely affect both major DNA repair mechanisms: base excision repair (BER) and nucleotide excision repair (NER). The aims of the present study were to (i) compare the genotoxicity of TiO2-NPs and their impact on DNA repair processes on A549 alveolar carcinoma and BEAS-2B normal bronchial lung cell lines and (ii) delve deeper into the mechanisms leading to these effects...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27798195/diet-sourced-carbon-based-nanoparticles-induce-lipid-alterations-in-tissues-of-zebrafish-danio-rerio-with-genomic-hypermethylation-changes-in-brain
#18
Eva Gorrochategui, Junyi Li, Nigel J Fullwood, Guang-Guo Ying, Meiping Tian, Li Cui, Heqing Shen, Sílvia Lacorte, Romà Tauler, Francis L Martin
With rising environmental levels of carbon-based nanoparticles (CBNs), there is an urgent need to develop an understanding of their biological effects in order to generate appropriate risk assessment strategies. Herein, we exposed zebrafish via their diet to one of four different CBNs: C60 fullerene (C60), single-walled carbon nanotubes (SWCNT), short multi-walled carbon nanotubes (MWCNTs) or long MWCNTs. Lipid alterations in male and female zebrafish were explored post-exposure in three target tissues (brain, gonads and gastrointestinal tract) using 'omic' procedures based in liquid chromatography coupled with mass spectrometry (LC-MS) data files...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27794034/impact-of-nanoparticles-on-dna-repair-processes-current-knowledge-and-working-hypotheses
#19
REVIEW
Marie Carriere, Sylvie Sauvaigo, Thierry Douki, Jean-Luc Ravanat
The potential health effects of exposure to nanomaterials (NMs) is currently heavily studied. Among the most often reported impact is DNA damage, also termed genotoxicity. While several reviews relate the DNA damage induced by NMs and the techniques that can be used to prove such effects, the question of impact of NMs on DNA repair processes has never been specifically reviewed. The present review article proposes to fill this gap of knowledge by critically describing the DNA repair processes that could be affected by nanoparticle (NP) exposure, then by reporting the current state of the art on effects of NPs on DNA repair, at the level of protein function, gene induction and post-transcriptional modifications, and taking into account the advantages and limitations of the different experimental approaches...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27789654/titanium-dioxide-food-additive-e171-induces-ros-formation-and-genotoxicity-contribution-of-micro-and-nano-sized-fractions
#20
Héloïse Proquin, Carolina Rodríguez-Ibarra, Carolyn G J Moonen, Ismael M Urrutia Ortega, Jacob J Briedé, Theo M de Kok, Henk van Loveren, Yolanda I Chirino
Since 1969, the European Union approves food-grade titanium dioxide (TiO2), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO2 fractions to these effects...
January 2017: Mutagenesis
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