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Gabriela Elibio Fagundes, Tamires Pavei Macan, Paula Rohr, Adriani Paganini Damiani, Franciani Rodrigues Da Rocha, Maiara Pereira, Luiza Martins Longaretti, Thais Ceresér Vilela, Luciane Bisognin Ceretta, Carolini Mendes, Paulo Cesar Lock Silveira, João Paulo Fernandes Teixeira, Vanessa Moraes de Andrade
No abstract text is available yet for this article.
March 11, 2019: Mutagenesis
Kei-Ichi Sugiyama, Hiroko Furusawa, Petr Grúz, Mawo Kinoshita, Masamitsu Honma
The mycotoxin ochratoxin A (OTA) is considered to be a human carcinogen. However, the mode of its carcinogenetic action has not been elucidated. Recently, it has become evident that epigenetic changes influence the risk of developing cancer. Since it has been revealed that the yeast flocculation displayed by the strains transformed with human DNA methyltransferases (DNMT) can be regulated by epigenetic mechanisms, we examined the effect of OTA on the transcription level of FLO1, which mediates the flocculation phenotype...
March 10, 2019: Mutagenesis
Ditte Marie Jensen, Mille Løhr, Majid Sheykhzade, Jens Lykkesfeldt, Regitze Sølling Wils, Steffen Loft, Peter Møller
Vegetable carbon (E153) and titanium dioxide (E171) are widely used as black and white food colour additives. The aim of this study was to assess gastrointestinal tight junction and systemic genotoxic effects in rats following exposure to E153 and E171 for 10 weeks by oral gavage once a week. The expression of tight junction proteins was assessed in intestinal tissues. Levels of DNA strand breaks, oxidatively damaged DNA and telomere length were assessed in secondary organs. Hydrodynamic suspensions of E153 and E173 indicated mean particles sizes of 230 and 270 nm, respectively, and only E153 gave rise to intracellular production of reactive oxygen species in colon epithelial (Caco-2) cells...
March 10, 2019: Mutagenesis
Pavel Rossner, Helena Libalova, Tereza Cervena, Kristyna Vrbova, Fatima Elzeinova, Alena Milcova, Andrea Rossnerova, Zuzana Novakova, Miroslav Ciganek, Michaela Pokorna, Antonin Ambroz, Jan Topinka
Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F2t-isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fibroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2...
March 10, 2019: Mutagenesis
Shizhi Wang, Haixia Zhu, Bo Ding, Xinrui Feng, Wenxuan Zhao, Mengjing Cui, Yuling Xu, Minxin Shi, Jian Chen, Hua Jin
Because genetic variants in microRNAs (miRNAs) or their surrounding regions can alter miRNA processing, expression and final biological function, we investigated whether miRNA single-nucleotide polymorphisms (SNPs) are associated with cervical cancer (CC) susceptibility. Common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, miR-499 rs3746444, miR-605 rs2043556 and miR-618 rs2682818) were genotyped in the 954 patients and 1339 controls. The results showed that the miR-149 rs2292832 TC/CC genotypes were associated with a 21% increased risk of CC compared with the TT genotype [odds ratio (OR) = 1...
March 10, 2019: Mutagenesis
Archana Panyala, Srinivas Chinde, Srinivas Indu Kumari, Mohammad Fazlur Rahman, Mohammed Mahboob, Jerald Mahesh Kumar, Paramjit Grover
Despite their enormous advantages, nanoparticles (NPs) have elicited disquiet over their safety. Among the numerous NPs, yttrium oxide (Y2O3) NPs are utilised in many applications. However, knowledge about their toxicity is limited, and it is imperative to investigate their potential adverse effects. Therefore, this study explored the effect of 28 days of repeated oral exposure of Wistar rats to 30, 120 and 480 mg/kg body weight (bw) per day of Y2O3 NPs and microparticles (MPs). Before initiation of the study, characterisation of the particles by transmission electron microscopy, dynamic light scattering, Brunauer-Emmett-Teller and laser Doppler velocimetry was undertaken...
February 9, 2019: Mutagenesis
Gabriela Elibio Fagundes, Tamires Pavei Macan, Paula Rohr, Adriani Paganini Damiani, Franciani Rodrigues Da Rocha, Maiara Pereira, Luiza Martins Longaretti, Thais Ceresér Vilela, Luciane Bisognin Ceretta, Carolini Mendes Silveira, Paulo Cesar Lock Silveira, João Paulo Fernandes Teixeira, Vanessa Moraes de Andrade
Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina...
February 6, 2019: Mutagenesis
Matteo Vian, Giuseppa Raitano, Alessandra Roncaglioni, Emilio Benfenati
Bacterial reverse mutation test is one of the most common methods used to address genotoxicity. The experimental test is designed to include a step to simulate mammalian metabolism. The most common metabolic activation system is the incubation with S9 fraction prepared from the livers of rodents. Usually, in silico models addressing this endpoint are developed on the basis of an overall call disregarding the fact that the toxic effect was observed before or after metabolic activation. Here, we present a new in silico model to predict mutagenicity as measured by activity in the bacterial reverse mutation test, bearing in mind the role of S9 activation to stimulate metabolism...
February 4, 2019: Mutagenesis
(no author information available yet)
No abstract text is available yet for this article.
March 6, 2019: Mutagenesis
Junichi Fukuchi, Airi Kitazawa, Keiji Hirabayashi, Masamitsu Honma
The International Council for Harmonisation of Technical Requirement for Pharmaceuticals for Human Use (ICH) M7 guideline on 'Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk' provides the application of two types of quantitative structure-activity relationship (QSAR) systems (rule- and statistics-based) as an alternative to the Ames test for evaluating the mutagenicity of impurities in pharmaceuticals. M7 guideline also states that the expert reviews can be applied when the outcomes of the two QSAR analyses show any conflicting or inconclusive prediction...
January 23, 2019: Mutagenesis
Azeddine Elhajouji, Dagmara Vaskova, Rebecca Downing, Stephen D Dertinger, Hansjeorg Martus
No abstract text is available yet for this article.
December 27, 2018: Mutagenesis
Hanns Moshammer, Abdul Wali Khan, Peter Wallner, Michael Poteser, Michael Kundi, Hans-Peter Hutter
Higher rates of nuclear anomalies in buccal cells of coffee workers exposed to pesticides in comparison to their unexposed peers were detected in our field study. Here, we extend our findings by examining other exposure indicators in this sample. Occupational exposure of 38 exposed and 33 non-exposed farmworkers was assessed as exposure days in the last month (0-25 days) and as years of exposure (0-47 years). Genotoxic and cytotoxic markers in buccal cells were analysed following standard procedures for buccal micronucleus cytome assay...
December 26, 2018: Mutagenesis
Shun Matsuda, Sayaka Wanibuchi, Toshihiko Kasahara
Ser139-phosphorylated H2AX (γH2AX) is a functional biomarker of DNA double-strand breaks. However, its conventional detection for in vivo samples relies on immunological methods using anti-γH2AX antibodies, making quantitative analysis difficult. Here, we established an absolute γH2AX quantification in vivo method for multiple organs in mice using liquid chromatography-triple quadrupole tandem mass spectrometry. When applying the method to male Institute of Cancer Research (ICR) mice (8 weeks old), the testes showed the highest γH2AX level (2...
December 24, 2018: Mutagenesis
Weiying Liu, Jing Xi, Yiyi Cao, Xinyue You, Ruixue Chen, Xinyu Zhang, Li Han, Guoyu Pan, Yang Luan
Metabolic activation is essential in standard in vitro genotoxicity test systems. At present, there is a lack of suitable cell models that can express the major characteristics of liver function for predicting substance toxicity in humans. Human-induced hepatocytes (hiHeps), which have been generated from fibroblasts by lentiviral expression of liver transcription factors, can express hepatic gene programs and can be expanded in vitro and display functional characteristics of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance...
December 24, 2018: Mutagenesis
Yurika Fujita, Hiroshi Honda, Masayuki Yamane, Takeshi Morita, Tomonari Matsuda, Osamu Morita
Genotoxicity evaluation has been widely used to estimate the carcinogenicity of test substances during safety evaluation. However, the latest strategies using genotoxicity tests give more weight to sensitivity; therefore, their accuracy has been very low. For precise carcinogenicity evaluation, we attempted to establish an integrated testing strategy for the tailor-made carcinogenicity evaluation of test materials, considering the relationships among genotoxicity test results (Ames, in vitro mammalian genotoxicity and in vivo micronucleus), carcinogenicity test results and chemical properties (molecular weight, logKow and 179 organic functional groups)...
December 14, 2018: Mutagenesis
Ulf Norinder, Ernst Ahlberg, Lars Carlsson
Valid and predictive models for classifying Ames mutagenicity have been developed using conformal prediction. The models are Random Forest models using signature molecular descriptors. The investigation indicates, on excluding not-strongly mutagenic compounds (class B), that the validity for mutagenic compounds is increased for the predictions based on both public and the Division of Genetics and Mutagenesis, National Institute of Health Sciences of Japan (DGM/NIHS) data while less so when using only the latter data source...
December 12, 2018: Mutagenesis
Srambikkal Nishad, Anu Ghosh
There remain significant uncertainties in estimation of risks with low doses of radiation. The small coastal belt in the southwestern state of Kerala, India, extending from Neendakara in the south to Purakkad in the north is one of the most extensively studied high-level natural background radiation areas (HLNRAs) of the world to address these concerns. The natural radioactivity here is due to occurrence of monazite sand bearing placer deposits along the coastline. In this study, proteomic approach was employed to study the response of human peripheral blood mononuclear cells (PBMCs) from individuals residing in HLNRA (N = 10; mean radiation dose: 15...
November 29, 2018: Mutagenesis
Olgica Mihaljevic, Snezana Zivancevic-Simonovic, Olivera Milosevic-Djordjevic, Predrag Djurdjevic, Danijela Jovanovic, Zeljko Todorovic, Darko Grujicic, Marina Radovic-Jakovljevic, Jovana Tubic, Aleksandra Markovic, Milan Paunovic, Marijana Stanojevic-Pirkovic, Slavica Markovic
As apoptosis and genome instability in children with autoimmune diseases (AIDs) are insufficiently investigated, we aimed to analyse them in peripheral blood lymphocytes (PBLs) of children and adolescents with Hashimoto's thyroiditis (HT), Graves' disease (GD) and type 1 diabetes mellitus (T1DM), including possible factors that could affect their occurrence. The study population included 24 patients and 19 healthy controls. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. Genome instability was measured as micronuclei (MNs) frequency using the cytokinesis-block MN assay...
November 27, 2018: Mutagenesis
Petko I Petkov, Terry W Schultz, Masamitsu Honma, Takashi Yamada, Elena Kaloyanova, Ovanes G Mekenyan
This study validates the performance of the TIssue MEtabolism Simulator (TIMES) genotoxicity models with data on pesticide chemicals included in a recently released European Food Safety Authority (EFSA) genotoxicity database. The EFSA database is biased towards negative chemicals. A comparison of substances included in the EFSA database and TIMES genotoxicity databases showed that the majority of the EFSA pesticides is not included in the TIMES genotoxicity databases and, thus, out of the applicability domains of the current TIMES models...
November 16, 2018: Mutagenesis
Masamitsu Honma, Airi Kitazawa, Alex Cayley, Richard V Williams, Chris Barber, Thierry Hanser, Roustem Saiakhov, Suman Chakravarti, Glenn J Myatt, Kevin P Cross, Emilio Benfenati, Giuseppa Raitano, Ovanes Mekenyan, Petko Petkov, Cecilia Bossa, Romualdo Benigni, Chiara Laura Battistelli, Alessandro Giuliani, Olga Tcheremenskaia, Christine DeMeo, Ulf Norinder, Hiromi Koga, Ciloy Jose, Nina Jeliazkova, Nikolay Kochev, Vesselina Paskaleva, Chihae Yang, Pankaj R Daga, Robert D Clark, James Rathman
The International Conference on Harmonization (ICH) M7 guideline allows the use of in silico approaches for predicting Ames mutagenicity for the initial assessment of impurities in pharmaceuticals. This is the first international guideline that addresses the use of quantitative structure-activity relationship (QSAR) models in lieu of actual toxicological studies for human health assessment. Therefore, QSAR models for Ames mutagenicity now require higher predictive power for identifying mutagenic chemicals. To increase the predictive power of QSAR models, larger experimental datasets from reliable sources are required...
October 23, 2018: Mutagenesis
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