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Genotoxicity

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https://www.readbyqxmd.com/read/29785231/advantages-of-evaluating-%C3%AE-h2ax-induction-in-non-clinical-drug-development
#1
REVIEW
Shigeki Motoyama, Akira Takeiri, Kenji Tanaka, Asako Harada, Kaori Matsuzaki, Junko Taketo, Saori Matsuo, Etsuko Fujii, Masayuki Mishima
γH2AX, the phosphorylated form of a histone variant H2AX at Ser 139, is already widely used as a biomarker to research the fundamental biology of DNA damage and repair and to assess the risk of environmental chemicals, pollutants, radiation, and so on. It is also beginning to be used in the early non-clinical stage of pharmaceutical drug development as an in vitro tool for screening and for mechanistic studies on genotoxicity. Here, we review the available information on γH2AX-based test systems that can be used to develop drugs and present our own experience of practically applying these systems during the non-clinical phase of drug development...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#2
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784397/a-novel-sample-preparation-procedure-for-effect-directed-analysis-of-micro-contaminants-of-emerging-concern-in-surface-waters
#3
Victoria Osorio, Merijn Schriks, Dennis Vughs, Pim de Voogt, Annemieke Kolkman
A novel sample preparation procedure relying on Solid Phase Extraction (SPE) combining different sorbent materials on a sequential-based cartridge was optimized and validated for the enrichment of 117 widely diverse contaminants of emerging concern (CECs) from surface waters (SW) and further combined chemical and biological analysis on subsequent extracts. A liquid chromatography coupled to high resolution tandem mass spectrometry LC-(HR)MS/MS protocol was optimized and validated for the quantitative analysis of organic CECs in SW extracts...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29783987/an-updated-review-of-the-genotoxicity-of-respirable-crystalline-silica
#4
REVIEW
Paul J A Borm, Paul Fowler, David Kirkland
Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review...
May 21, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29783948/expansion-of-the-sos-regulon-of-vibrio-cholerae-through-extensive-transcriptome-analysis-and-experimental-validation
#5
Evelyne Krin, Sebastian Aguilar Pierlé, Odile Sismeiro, Bernd Jagla, Marie-Agnès Dillies, Hugo Varet, Oihane Irazoki, Susana Campoy, Zoé Rouy, Stéphane Cruveiller, Claudine Médigue, Jean-Yves Coppée, Didier Mazel
BACKGROUND: The SOS response is an almost ubiquitous response of cells to genotoxic stresses. The full complement of genes in the SOS regulon for Vibrio species has only been addressed through bioinformatic analyses predicting LexA binding box consensus and in vitro validation. Here, we perform whole transcriptome sequencing from Vibrio cholerae treated with mitomycin C as an SOS inducer to characterize the SOS regulon and other pathways affected by this treatment. RESULTS: Comprehensive transcriptional profiling allowed us to define the full landscape of promoters and transcripts active in V...
May 21, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29783088/evaluation-of-genotoxicity-and-mutagenic-effects-of-vector-dna-nanocomplexes-in-transfected-mesenchymal-stem-cells-by-flow-cytometry
#6
Alireza Nomani, Xuguang Chen, Arash Hatefi
In recent years, there has been a great deal of interest in ex-vivo genetic modification of mesenchymal stem cells (MSCs) to meet various biomedical needs. Considering the self-renewal potential of MSCs, it is critically important to ensure that transfection vectors (gene carriers) do not induce genotoxicity because they could theoretically turn a single stem cell into a cancer-initiating cell. Unfortunately, there is currently no reliable, unbiased, and quantitative method to measure genotoxicity (micronuclei formation) of gene carriers directly in transfected MSCs...
May 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29780732/effect-of-fixed-metallic-oral-appliances-on-oral-health
#7
REVIEW
Ahmad Alnazzawi
There is a substantial proportion of the population using fixed metallic oral appliances, such as crowns and bridges, which are composed of various dental alloys. These restorations may be associated with a number of effects on oral health with variable degrees of severity, to review potential effects of using fixed metallic oral appliances, fabricated from various alloys. The MEDLINE/PubMed database was searched using certain combinations of keywords related to the topic. The search revealed that burning mouth syndrome, oral pigmentation, hypersensitivity and lichenoid reactions, and genotoxic and cytotoxic effects are the major potential oral health changes associated with fixed prosthodontic appliances...
March 2018: Journal of International Society of Preventive & Community Dentistry
https://www.readbyqxmd.com/read/29779429/genotoxicity-evaluation-of-carbon-monoxide-and-1-3-butadiene-using-a-new-joint-technology-the-in-vitro-%C3%AE-h2ax-hcs-assay-combined-with-air-liquid-interface-system
#8
Sen Zhang, Huan Chen, An Wang, Yong Liu, Hongwei Hou, Qingyuan Hu
To investigate the genotoxicity of gaseous toxicants CO and 1,3-butadiene in vitro, a novel combination technology-the in vitro γH2AX high content screening assay combined with air-liquid interface system was established. The results showed that this new technology was available and effective. Based on the joint technology, genotoxicity of CO and 1,3-butadiene was evaluated further in this study. The results showed that treatment concentrations (0, 20%,40%, 80% and 100%, v/v) and exposure time (15, 30, 45, 60 and 90 min) of CO both had no statistically significant effects on the induction of γH2AX (p > 0...
May 21, 2018: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29778644/a-trichostatin-a-tsa-sp1-mediated-mechanism-for-the-regulation-of-sall2-tumor-suppressor-in-jurkat-t-cells
#9
Matías I Hepp, David Escobar, Carlos Farkas, Viviana Hermosilla, Claudia Álvarez, Roberto Amigo, José L Gutiérrez, Ariel F Castro, Roxana Pincheira
SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777725/strain-related-differences-in-mouse-lung-gene-expression-over-a-two-year-period-of-inhalation-exposure-to-styrene-relevance-to-human-risk-assessment
#10
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol E Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Debra B Layko, Patrick D McMullen
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(-/-) knockout (C57BL/6-KO) and a Cyp2F1/2A13/2B6 transgenic mouse (C57BL/6-TG). With short term exposures (1-day to 1-week), CD-1 and C57BL/6-WT mice had thousands of differentially expressed genes (DEGs), consistent with changes in pathways for cell proliferation, cellular lipid metabolism, DNA-replication and inflammation...
May 16, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29777724/novel-mirna-biomarkers-for-genotoxicity-screening-in-mouse
#11
Hiroyuki Oka, Koichi Masuno, Takeki Uehara, Toru Okamoto, Yoshiharu Matsuura, Toru Nakano, Shinpei Yamaguchi
The genotoxic potential of drugs is a serious problem, and its evaluation is one of the most critical processes of drug development. Although the comet assay of compound-exposed tissue is a frequently used genotoxicity test, its high false-positive rate is a major complication, and we consistently obtained false-positive results using the comet assay of mouse liver for nine hepatotoxic non-genotoxins (NGTXs). To identify novel genotoxin (GTX)-specific biomarkers, we screened the expression of 750 microRNAs (miRNAs) in the livers of mice treated with GTXs or NGTXs...
May 16, 2018: Toxicology
https://www.readbyqxmd.com/read/29775721/critical-evaluation-of-2-ethylhexyl-acrylate-dermal-carcinogenicity-studies-using-contemporary-criteria
#12
REVIEW
Sandra Murphy, Robert Ellis-Hutchings, Lavorgie Finch, Stefanie Welz, Karin Wiench
Skin tumors have been observed in C3H/HeJ mice following treatment with high and strongly irritating concentrations of 2-ethylhexyl acrylate (2-EHA). Dermal carcinogenicity studies performed with 2-EHA are reviewed, contrasting the results in two mouse strains (C3H/HeJ and NMRI) under different dosing regimens. Application of contemporary evaluation criteria to the existing dermal carcinogenicity dataset demonstrates that 2-EHA induces skin tumors only at concentrations exceeding an maximum tolerated dose (MTD) and in the immune-dysregulated C3H/HeJ mouse model...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29773172/seleno-l-methionine-and-l-ascorbic-acid-differentiate-the-biological-activity-of-doxorubicin-and-its-metal-complexes-as-a-new-anticancer-drugs-candidate
#13
Marzena Matejczyk, Grzegorz Świderski, Renata Świsłocka, Stanisław Józef Rosochacki, Włodzimierz Lewandowski
The most important problems of anti-cancer therapy include the toxicity of the drugs applied to healthy cells and the multi-drug cells resistance to chemotherapeutics. One of the most commonly used anticancer drugs is doxorubicin (DOX) used to treat certain leukemias and non-Hodgkin's lymphomas, as well as bladder, breast, stomach, lung, ovarian, thyroid, multiple myeloma and other cancers. Preliminary studies showed that metal complex with DOX improve its cytostatic activity with changes in their molecular structure and distribution of electrons, resulting in a substantial change of its biological activity (including antitumor activity)...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772987/alumina-biocompatibility
#14
Eric Denes, Guislaine Barrière, Evelyne Poli, Guillaume Lévêque
Alumina (Al2O3) ceramic is widely used for medical devices and its biocompatibility is well known and is reported in articles and textbooks. However, finding proof of this assertion gathered over more than 40 years can be challenging. We performed a literature review about alumina biocompatibility to compile data from the literature. We searched for articles on the biocompatibility of alumina in relation to the ISO 10993-1 International Standard, which defines the biocompatibility of biomaterials. For every biological effect listed in the norm, such as cytotoxicity, sensitization, implantation, and genotoxicity, in vitro and in vivo tests in animals and humans did not reveal any abnormal biological response...
2018: Journal of Long-term Effects of Medical Implants
https://www.readbyqxmd.com/read/29772712/inhibition-of-human-immunodeficiency-virus-type-1-entry-by-a-keggin-polyoxometalate
#15
Xiaoli Wang, Jiao Wang, Wenmei Zhang, Boye Li, Ying Zhu, Qin Hu, Yishu Yang, Xiaoguang Zhang, Hong Yan, Yi Zeng
Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K₆HPTi₂W10 O40 ). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus...
May 16, 2018: Viruses
https://www.readbyqxmd.com/read/29772356/assessment-of-toxicity-and-differential-antimicrobial-activity-of-methanol-extract-of-rhizome-of-simaba-ferruginea-a-st-hil-and-its-isolate-canthin-6-one
#16
Vanessa Fátima Gazoni, Sikiru Olaitan Balogun, Karuppusamy Arunacham, Darley Maria Oliveira, Valdir Cechinel Filho, Samara Rosolem Lima, Edson Moleta Colodel, Ilsamar Mendes Soares, Sérgio Donizeti Ascêncio, Domingos Tabajara de Oliveira Martins
ETHNOPHARMACOLOGICAL RELEVANCE: Simaba ferruginea A. St.-Hil., Simaroubaceae, popularly known as "calunga" is a typical subtropical shrub used in Central Brazil mainly for infection, anti-inflammatory, analgesic and gastric duodenal-ulcers. It presents in its composition the alkaloid canthin-6-one, an alkaloid indole β-carboxylic. AIM: This study aims to investigate the toxicity, antimicrobial activities of methanol extract of Simaba ferruginea (MESf) and canthin-6-one by using different experimental models...
May 14, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29772267/reactive-oxygen-species-independent-genotoxicity-of-indium-tin-oxide-nanoparticles-triggered-by-intracellular-degradation
#17
Yosuke Tabei, Sakiko Sugino, Yoshihiro Nakajima, Masanori Horie
No abstract text is available yet for this article.
May 14, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29770949/selenium-ameliorates-afb-1-induced-excess-apoptosis-in-chicken-splenocytes-through-death-receptor-and-endoplasmic-reticulum-pathways
#18
Jing Fang, Panpan Zhu, Zhuangzhi Yang, Xi Peng, Zhicai Zuo, Hengmin Cui, Ping Ouyang, Gang Shu, Zhengli Chen, Chao Huang, Wentao Liu
Aflatoxin B1 (AFB1 ) can cause hepatotoxicity, genotoxicity, and immunosuppressive effects for a variety of organisms. Selenium (Se), as an essential nutrient element, plays important protective effects against cell apoptosis induced by AFB1 . This research aimed to reveal the ameliorative effects of selenium on AFB1 -induced excess apoptosis in chicken splenocytes through death receptor and endoplasmic reticulum pathways in vivo. Two hundred sixteen neonatal chickens, randomized into four treatments, were fed with basal diet (control treatment), 0...
May 16, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29768882/grape-seed-extract-alone-or-combined-with-atropine-in-treatment-of-malathion-induced-neuro-and-genotoxicity
#19
Omar M E Abdel-Salam, Asmaa F Galal, Mahrousa M Hassanane, Lamiaa M Salem, Somaia A Nada, Fatma A Morsy
The aim of this study was to investigate the effect of treatment with grape seed extract (GSE) on the neurotoxic and genotoxic effects of acute malathion exposure. Rats received malathion (150 mg/kg by i.p. injection) for two successive days alone or combined with GSE at doses of 150 or 300 mg/kg, orally or with GSE at 300 mg/kg and atropine at a dose of 2 mg/kg, i.p. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase (PON1) were determined in cortex, striatum, and rest of brain tissue (subcortex)...
January 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29768880/tio%C3%A2-nps-induce-dna-damage-in-lymphocytes-from-healthy-individuals-and-patients-with-respiratory-diseases-an-ex-vivo-in-vitro-study
#20
Ilham F Osman, Mojgan Najafzadeh, Vyom Sharma, Ritesh K Shukla, B K Jacob, Alok Dhawan, D Anderson
Little is known of the effects of nanoparticles in human systems, let alone in diseased individuals and nanotechnology has preceded nanotoxicology. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases [lung cancer, chronic obstructive pulmonary disease (COPD) and asthma] were compared with those in healthy Individuals, to determine differences in sensitivity to nanochemical insult. The Comet assay was performed according to recommended guidelines...
January 1, 2018: Journal of Nanoscience and Nanotechnology
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