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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
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
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
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
Douglas G Wright, Reneau Castore, Runhua Shi, Amrita Mallick, Don G Ennis, Lynn Harrison
Mycobacterium tuberculosis and Mycobacterium smegmatis express a Ku protein and a DNA ligase D and are able to repair DNA double strand breaks (DSBs) by non-homologous end-joining (NHEJ). This pathway protects against DNA damage when bacteria are in stationary phase. Mycobacterium marinum is a member of this mycobacterium family and like M. tuberculosis is pathogenic. M. marinum lives in water, forms biofilms and infects fish and frogs. M. marinum is a biosafety level 2 (BSL2) organism as it can infect humans, although infections are limited to the skin...
September 9, 2016: Mutagenesis
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...
August 30, 2016: Mutagenesis
Yan Li, Shareen H Doak, Jian Yan, David H Chen, Min Zhou, Roberta A Mittelstaedt, Ying Chen, Chun Li, Tao Chen
A number of in vitro methodologies have been used to assess the genotoxicity of different nanomaterials, including titanium dioxide nanoparticles (TiO2 NPs) and silver nanoparticles (AgNPs). The in vitro micronucleus assay is one of the most commonly used test methods for genotoxicity evaluation of nanomaterials. However, due to the novel features of nanomaterials, such as high adsorption capacity and fluorescence properties, there are unexpected interactions with experimental components and detection systems...
August 27, 2016: Mutagenesis
Bryant C Nelson, Christa W Wright, Yuko Ibuki, Maria Moreno-Villanueva, Hanna L Karlsson, Giel Hendriks, Christopher M Sims, Neenu Singh, Shareen H Doak
The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs...
August 26, 2016: Mutagenesis
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...
August 22, 2016: Mutagenesis
Andrea Borghini, Martin Roursgaard, Maria Grazia Andreassi, Ali Kermanizadeh, Peter Møller
One type of carbon nanotubes (CNTs) (MWCNT-7, from Mitsui) has been classified as probably carcinogenic to humans, however insufficient data does not warrant the same classification for other types of CNTs. Experimental data indicate that CNT exposure can result in oxidative stress and DNA damage in cultured cells, whereas these materials appear to induce low or no mutagenicity. Therefore, the present study aimed to investigate whether in vitro exposure of cultured airway epithelial cells (A549) to multi-walled CNTs (MWCNTs) could increase the DNA repair activity of oxidatively damaged DNA and drive the cells toward replicative senescence, assessed by attrition of telomeres...
August 16, 2016: Mutagenesis
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...
August 16, 2016: Mutagenesis
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...
August 10, 2016: Mutagenesis
Linda Rieswijk, Karen J J Brauers, Maarten L J Coonen, Danyel G J Jennen, Simone G J van Breda, Jos C S Kleinjans
The well-defined battery of in vitro systems applied within chemical cancer risk assessment is often characterised by a high false-positive rate, thus repeatedly failing to correctly predict the in vivo genotoxic and carcinogenic properties of test compounds. Toxicogenomics, i.e. mRNA-profiling, has been proven successful in improving the prediction of genotoxicity in vivo and the understanding of underlying mechanisms. Recently, microRNAs have been discovered as post-transcriptional regulators of mRNAs. It is thus hypothesised that using microRNA response-patterns may further improve current prediction methods...
September 2016: Mutagenesis
Mirzakarim Karimovich Alchinbayev, Araylyim Nugmanovna Aralbayeva, Lazzat Namatullaevna Tuleyeva, Svetlana Melsovna Duysenbayeva, Marat Abzalovich Makazhanov
Male infertility is a relevant social and medical problem. Male infertility is mostly caused by genetic disorders. The purpose of the study was to analyze the correlation of chromosome aberrations, as well as DNA fragmentation and various manifestations of spermatogenesis disorder. Sperm samples of 58 males with infertility and 23 conditionally healthy males were studied. All patients diagnosed with asthenozoospermia, teratozoospermia, oligoasthenozoospermia and oligoteratozoospermia underwent subsequent analysis of sperm DNA fragmentation...
September 2016: Mutagenesis
Nilton C N Santos, Maria E S P Ramos, Aline F B Ramos, Adriana B Cerqueira, Eneida M M Cerqueira
Pulp therapy is the last resort for preserving deciduous teeth. However, the genotoxic and cytotoxic effects of many products used in this therapy are not well established. The aim of this study was to use the micronucleus test on bone marrow from mice to evaluate the genotoxic and cytotoxic effects of four filling pastes: zinc oxide, calcium hydroxide P.A., mineral trioxide aggregate and an iodoform paste (iodoform + camphorated + paramonochlorophenol + rifamycin + prednisolone). Male Swiss mice were divided into 4 groups of 10 animals, each exposed to one of the pastes, and were subdivided according to the dilutions tested: 1/10, 1/50, 1/500 and 1/1000 administered intraperitoneally (0...
September 2016: Mutagenesis
Gyöngyi Farkas, Zsolt Jurányi, Gábor Székely, Zsuzsa S Kocsis, Sarolta Gundy
Numerical and structural chromosomal abnormalities are the hallmarks of cancer. Whereas the structural chromosome aberrations got more substantial attention for cancer risk assessment in a healthy population, the role of aneuploidy is much less understood in this respect. We analysed the frequency of numerical (and structural) aberrations in peripheral blood lymphocytes of 2145 healthy individuals between 1989 and 2010, taking into account different biological- and exposure-conditions. We also studied to what extent chromosome gains or losses may predict the probability of cancer...
September 2016: Mutagenesis
Minor P Huffman, Anja H Høie, Camilla Svendsen, Gunnar Brunborg, Michael Murkovic, Hansruedi Glatt, Trine Husøy
2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA...
September 2016: Mutagenesis
Leena Rivina, Michael J Davoren, Robert H Schiestl
Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary...
September 2016: Mutagenesis
Bhavuk Garg, Gaurav Pathria, Christine Wagner, Margarita Maurer, Stephan N Wagner
Current therapy approaches in melanoma targeting have met with the development of resistance and tumour recurrence with a more aggressive phenotype. In a quest for alternative therapy targets, we had previously identified Signal Sequence Receptor 2 (SSR2) as a gene with high expression in a subgroup of human primary melanomas. Now we show that SSR2 exerts a prosurvival functionality in human melanoma cells and that high expression levels of SSR2 are associated with an unfavourable disease outcome in primary melanoma patients...
September 2016: Mutagenesis
Alessandra Iannuzzi, Angela Perucatti, Viviana Genualdo, Alfredo Pauciullo, Rita Melis, Claudio Porqueddu, Mauro Marchetti, Marianna Usai, Leopoldo Iannuzzi
Furocoumarin extracts from Psoralea morisiana, the endemic Sardinian legume species, were tested for their mutagenic potential on river buffalo blood cells. The results obtained performing the sister chromatid exchange (SCE) test in blood cultures of five river buffalo calves (exposure to furocoumarins for 72h) and five cows (exposure to furocoumarins for 3h, in the absence and presence of S9 metabolic activator) are reported. Significant differences in mean values of SCEs were observed in cells of calves compared to control cells (unexposed), but no differences in SCE mean values were found between treated and untreated cells of cows in the presence or absence of S9...
September 2016: Mutagenesis
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