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Mutagenesis

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https://www.readbyqxmd.com/read/27932515/genotoxic-effect-of-iron-overload-and-disease-complications-in-transfused-%C3%AE-thalassaemic-patients
#1
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/27864332/weak-silica-nanomaterial-induced-genotoxicity-can-be-explained-by-indirect-dna-damage-as-shown-by-the-ogg1-modified-comet-assay-and-genomic-analysis
#2
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...
November 17, 2016: 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
#3
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...
November 12, 2016: 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
#4
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...
November 10, 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
#5
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
#6
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/27815329/critical-review-of-the-current-and-future-challenges-associated-with-advanced-in-vitro-systems-towards-the-study-of-nanoparticle-secondary-genotoxicity
#7
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...
November 4, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27803034/comparison-of-the-dna-damage-response-in-beas-2b-and-a549-cells-exposed-to-titanium-dioxide-nanoparticles
#8
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...
November 1, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27794034/impact-of-nanoparticles-on-dna-repair-processes-current-knowledge-and-working-hypotheses
#9
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...
October 28, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27789654/titanium-dioxide-food-additive-e171-induces-ros-formation-and-genotoxicity-contribution-of-micro-and-nano-sized-fractions
#10
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...
October 27, 2016: 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
#11
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...
October 26, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27760801/toxicogenomics-analysis-of-mouse-lung-responses-following-exposure-to-titanium-dioxide-nanomaterials-reveal-their-disease-potential-at-high-doses
#12
Luna Rahman, Dongmei Wu, Michael Johnston, Andrew William, Sabina Halappanavar
Titanium dioxide nanoparticles (TiO2NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO2NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO2NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO2NPs...
October 19, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27671865/inter-laboratory-consistency-and-variability-in-the-buccal-micronucleus-cytome-assay-depends-on-biomarker-scored-and-laboratory-experience-results-from-the-humnxl-international-inter-laboratory-scoring-exercise
#13
Claudia Bolognesi, Siegfried Knasmueller, Armen Nersesyan, Paola Roggieri, Marcello Ceppi, Marco Bruzzone, Ewa Blaszczyk, Danuta Mielzynska-Svach, Mirta Milic, Stefano Bonassi, Danieli Benedetti, Juliana Da Silva, Raphael Toledo, Daisy Maria Fávero Salvadori, Helena Groot de Restrepo, Metka Filipic, Klara Hercog, Ayça Aktaş, Sema Burgaz, Michael Kundi, Tamara Grummt, Philip Thomas, Maryam Hor, Maria Escudero-Fung, Nina Holland, Michael Fenech
The buccal micronucleus cytome (BMNcyt) assay in uncultured exfoliated epithelial cells from oral mucosa is widely applied in biomonitoring human exposures to genotoxic agents and is also proposed as a suitable test for prescreening and follow-up of precancerous oral lesions. The main limitation of the assay is the large variability observed in the baseline values of micronuclei (MNi) and other nuclear anomalies mainly related to different scoring criteria. The aim of this international collaborative study, involving laboratories with different level of experience, was to evaluate the inter- and intra-laboratory variations in the BMNcyt parameters, using recently implemented guidelines, in scoring cells from the same pooled samples obtained from healthy subjects (control group) and from cancer patients undergoing radiotherapy (treated group)...
September 26, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27658823/surface-modification-does-not-influence-the-genotoxic-and-inflammatory-effects-of-tio2-nanoparticles-after-pulmonary-exposure-by-instillation-in-mice
#14
Håkan Wallin, Zdenka O Kyjovska, Sarah S Poulsen, Nicklas R Jacobsen, Anne T Saber, Stefan Bengtson, Petra Jackson, Ulla Vogel
The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure...
September 22, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27658822/fibrous-shape-underlies-the-mutagenic-and-carcinogenic-potential-of-nanosilver-while-surface-chemistry-affects-the-biosafety-of-iron-oxide-nanoparticles
#15
Alena Gábelová, Naouale El Yamani, Tamara Iglesias Alonso, Barbora Buliaková, Annamária Srančíková, Andrea Bábelová, Elise Runden Pran, Lise Marie Fjellsbø, Elisabeth Elje, Mazyar Yazdani, Maria João Silva, Mária Dušinská
Nowadays engineered nanomaterials (ENMs) are increasingly used in a wide range of commercial products and biomedical applications. Despite this, the knowledge of human potential health risk as well as comprehensive biological and toxicological information is still limited. We have investigated the capacity of two frequently used metallic ENMs, nanosilver and magnetite nanoparticles (MNPs), to induce thymidine kinase (Tk (+/-)) mutations in L5178Y mouse lymphoma cells and transformed foci in Bhas 42 cells. Two types of nanosilver, spherical nanoparticles (AgNM300) and fibrous (AgNM302) nanorods/wires, and MNPs differing in surface modifications [MNPs coated with sodium oleate (SO-MNPs), MNPs coated with SO + polyethylene glycol (SO-PEG-MNPs) and MNPs coated with SO + PEG + poly(lactide-co-glycolic acid) SO-PEG-PLGA-MNPs] were included in this study...
September 22, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27576335/silver-nanoparticles-exhibit-size-dependent-differential-toxicity-and-induce-expression-of-syncytin-1-in-fa-aml1-and-molt-4-leukaemia-cell-lines
#16
Sultan Alqahtani, Pawika Promtong, Anthony W Oliver, Xiaotong T He, Thomas D Walker, Andrew Povey, Lynne Hampson, Ian N Hampson
Human endogenous retrovirus (HERV) sequences make up ~8% of the human genome and increased expression of some HERV proteins has been observed in various pathologies including leukaemia and multiple sclerosis. However, little is known about the function of these HERV proteins or environmental factors which regulate their expression. Silver nanoparticles (AgNPs) are used very extensively as antimicrobials and antivirals in numerous consumer products although their effect on the expression of HERV gene products is unknown...
November 2016: Mutagenesis
https://www.readbyqxmd.com/read/27549112/epigenetic-mutagen-as-histone-modulator-can-be-detected-by-yeast-flocculation
#17
Kei-Ichi Sugiyama, Hiroko Furusawa, Masatomi Shimizu, Petr Grúz, Masamitsu Honma
We have previously reported that flocculation of a yeast co-transformed with the human DNA methyltransferase 1 (DNMT1) and DNMT3B genes was inhibited by DNMT inhibitors. It is well known that epigenetic mutagens can disturb nucleosome positioning via DNA methylation and/or histone modification. In this study we first examined the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the flocculation level of yeast. TSA dose-dependently promoted the flocculation exhibited by the yeast transformed with the DNMT genes or empty vectors...
November 2016: Mutagenesis
https://www.readbyqxmd.com/read/27530330/assessment-of-dna-damage-in-underground-coal-miners-using-the-cytokinesis-block-micronucleus-assay-in-peripheral-blood-lymphocytes
#18
Maxim Yu Sinitsky, Varvara I Minina, Nikolay I Gafarov, Maxim A Asanov, Aleksey V Larionov, Anastasia V Ponasenko, Valentin P Volobaev, Vladimir G Druzhinin
Coal miners are exposed to coal dust, containing mineral particles, inorganic compounds and polycyclic aromatic hydrocarbons, and to ionizing radiation. These factors can induce oxidative stress and promote inflammation that leads to DNA damage. The aim of this investigation is to analyse the degree of DNA damage in miners working in underground coal mines in Kemerovo Region (Russian Federation) using the cytokinesis-block micronucleus assay (CBMN) in peripheral blood lymphocytes. The exposed group included 143 coal miners (mean age = 50...
November 2016: Mutagenesis
https://www.readbyqxmd.com/read/27509906/runx2-mutation-impairs-bone-remodelling-of-dental-follicle-cells-and-periodontal-ligament-cells-in-patients-with-cleidocranial-dysplasia
#19
Xiangyu Sun, Xiaozhe Wang, Chenying Zhang, Yang Liu, Xiang Yang, Wenjuan Yan, Zhongning Liu, Yixiang Wang, Shuguo Zheng
RUNX2 is an important osteo-specific factor with crucial functions in bone formation and remodelling as well as resorption of teeth. Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth. In our study, dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were isolated, cultured and identified from one patient with CCD and compared with normal controls. This CCD patient was confirmed to have a heterozygous frameshift mutation of RUNX2 (c...
November 2016: Mutagenesis
https://www.readbyqxmd.com/read/27470700/ros-dependent-genotoxicity-cell-cycle-perturbations-and-apoptosis-in-mouse-bone-marrow-cells-exposed-to-formulated-mixture-of-cypermethrin-and-chlorpyrifos
#20
Lalit K S Chauhan, Meenu Varshney, Vibha Pandey, Preeti Sharma, Vipin K Verma, P Kumar, Sudhir K Goel
Swiss albino mice were exposed to formulated cypermethrin (CMR) and/or or chlorpyrifos (CPF) through oral gavages for 60 days. Test doses of CMR (0.69, 1.38 or 2.76mg/kg/day) or CPF (0.5, 1.0 or 2.0mg/kg/day) or CMR + CPF (0.69 + 0.5, 1.38 + 1.0 or 2.76 + 2.0mg/kg/day) were based on the acute oral median lethal doses of CMR or CPF. Chromosome aberrations (CA), micronucleus (MN) induction, cell cycle perturbations, apoptosis and reactive oxygen species (ROS) generation were analysed in bone marrow cells. To explore the involvement of ROS induction, HaCat cells were exposed in vitro to arbitrary concentrations of CMR and/or CPF...
November 2016: Mutagenesis
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