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Mutation Research

Yang Zou, Jiang-Yan Zhou, Jiu-Bai Guo, Li-Qun Wang, Yong Luo, Zi-Yu Zhang, Fa-Ying Liu, Jun Tan, Feng Wang, Ou-Ping Huang
Endometriosis is a potential premalignant disorder. The underlying molecular aberrations, however, are not fully understood. A recent exome sequencing study found that 25% (10/39) of deep infiltrating endometriosis harbored cancer driver gene mutations. However, it is unclear whether these mutations also exist in ovarian endometriosis. Here, a total of 101 ovarian endometriosis samples were analyzed for the presence of these gene mutations, including KRAS, PPP2R1A, PIK3CA and ARID1A. In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed...
March 9, 2018: Mutation Research
Shahid Chaudhary, Gorantla Venkata Raghuram, Indraneel Mittra
Recent research shows that extra-nuclear cell-free chromatin (cfCh) released from dying cells can freely enter into healthy cells and integrate into their genomes. Genomic integration of cfCh leads to dsDNA breaks and activation of inflammatory cytokines both of which occur concurrently with similar kinetics and that induction of inflammation can be abrogated by preventing DNA breaks with the use of cfCh inactivating agents. The proposal is put forward that inflammatory cytokines are a new family of DDR proteins that are activated following dsDNA breaks inflicted by genomic integration of cfCh...
February 22, 2018: Mutation Research
Zhiqiang Bai, Zhouhua Li, Wei Xiao
In this study, we report the identification and functional characterization of the Drosophila ben/ubc13 gene, encoding a unique ubiquitin-conjugating enzyme (Ubc or E2), in DNA-damage response. Ben forms a heterodimer with DmUev1a, the only Ubc/E2 variant (Uev) in Drosophila. Ben and DmUev1a act together to catalyze K63-linked polyubiquitination in vitro. ben can functionally rescue the yeast ubc13 null mutant from killing by DNA-damaging agents. We also find that BenP97S , which was previously described to affect the connectivity between the giant fiber and the tergotrochanter motor neuron, fails to interact with the RING protein Chfr but retains interaction with DmUev1a as well as Uevs from other species...
February 21, 2018: Mutation Research
Pawan Kumar Raghav, Ajay Kumar Singh, Gurudutta Gangenahalli
Several signaling pathways, ligands, and genes that regulate proliferative and self-renewal properties of the Hematopoietic Stem Cells (HSCs) have been studied meticulously. One of the signaling pathways that play a crucial role in the process of hematopoiesis is the Stem Cell Factor (SCF) mediated c-Kit pathway. The c-Kit is a Receptor Tyrosine Kinase (RTK), which is expressed in the cells including HSCs. It undergoes dimerization upon binding with its cognate ligand SCF. As a result, phosphorylation of the Juxtamembrane (JM) domain of c-Kit takes place at Tyr568 and Tyr570 residues...
February 17, 2018: Mutation Research
Miria Ricchetti
Mitochondrial DNA (mtDNA), which is essential for mitochondrial and cell function, is replicated and transcribed in the organelle by proteins that are entirely coded in the nucleus. Replication of mtDNA is challenged not only by threats related to the replication machinery and orchestration of DNA synthesis, but also by factors linked to the peculiarity of this genome. Indeed the architecture, organization, copy number, and location of mtDNA, which are markedly distinct from the nuclear genome, require ad hoc and complex regulation to ensure coordinated replication...
February 1, 2018: Mutation Research
Marek Adamowicz, Fabrizio d'Adda di Fagagna, Jelena Vermezovic
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) controls one of the most frequently used DNA repair pathways in a cell, the non-homologous end joining (NHEJ) pathway. However, the exact role of DNA-PKcs in NHEJ remains poorly defined. Here we show that NOTCH1 attenuates DNA-PKcs-mediated autophosphorylation, as well as the phosphorylation of its specific substrate XRCC4. Surprisingly, NOTCH1-expressing cells do not display any significant impairment in the DNA damage repair, nor cellular survival, and remain sensitive to small molecule DNA-PKcs inhibitor...
February 1, 2018: Mutation Research
Kazunari Hashiguchi, Michio Hayashi, Mutsuo Sekiguchi, Keiko Umezu
The hydrolysis of nucleotides containing 8-oxo-7,8-dihydroguanine (8-oxoG) is important in the maintenance of genome stability. Human cells possess three types of proteins, MTH1 (NUDT1), MTH2 (NUDT15) and MTH3 (NUDT18), which have the potential to hydrolyze deoxyribonucleoside di- and triphosphates containing 8-oxoG to the monophosphate, the form of which is unusable for DNA synthesis. To elucidate the physiological roles of these enzymes, we constructed single knockout (KO) cell lines for each of the MTH1, MTH2 and MTH3 genes and MTH1 and MTH2-double KO cell lines from the human HeLa S3 line using CRISPR/Cas9...
January 23, 2018: Mutation Research
Önder Aybastıer, Sam Dawbaa, Cevdet Demir, Oğuzhan Akgün, Engin Ulukaya, Ferda Arı
Lung cancer has a high treatment cost and poor prognosis in comparison to other types of cancers. This work was involved in studying oxidative DNA base damage inhibition. Accordingly, standard carvacrol, thymol, thymoquinone with water and water-methanol extract of thyme (Origanum vulgare L. subsp. hirtum (link.) Ietswaart), thyme oil and thyme water were prepared and investigated for their efficacy to inhibit DNA oxidative damage formed by H2O2 in malignant lung cells (A549). The antioxidant capacity by ABTS assay was 271...
January 20, 2018: Mutation Research
Lisa Wiesmüller, Karin Scharffetter-Kochanek, Hartmut Geiger
No abstract text is available yet for this article.
January 5, 2018: Mutation Research
M Monserrat Pacheco-Martínez, Elsa Cervantes-Ríos, María Del Carmen García-Rodríguez, Rocío Ortiz-Muñiz
Severe malnutrition is a complex condition that increases susceptibility to infections. Thus, drugs are extensively used in malnutrition cases. In the present study, we assessed the mutagenic effects of combined trimethoprim and sulfamethoxazole (TMP-SMX) treatment in undernourished (UN) and well-nourished (WN) rats. Six-week-old UN and WN Han-Wistar rats were treated with TMP-SMX at a daily dose of 10 mg/kg/d TMP and 50 mg/kg/d SMX for 5 or 10 days. Blood was collected from the tail vein one day before (day -1) and 15, 30, and 45 days after TMP-SMX administration...
December 30, 2017: Mutation Research
Larry D Claxton
No abstract text is available yet for this article.
April 2018: Mutation Research
D Thorne, M Hollings, A Seymour, J Adamson, A Dalrymple, M Ballantyne, M Gaca
There is a growing consensus that e-cigarettes hold the potential for reducing the harm associated with cigarette smoking. Recently published studies have reported in vitro testing of e-cigarettes, demonstrating reduced toxicological and biological effects. Few studies however have reported the use of e-cigarettes under extreme testing conditions. To assess the full mutagenic potential of a commercially available electronic-cigarette (Vype ePen), this study investigated the delivery of aerosol under extreme conditions, using a scaled-down 35 mm plate Ames bacterial reverse mutagenicity assay...
April 2018: Mutation Research
David Kirkland, Paul Fowler
Trimethylolpropane triacrylate (TMPTA) is a trifunctional acrylate monomer which polymerizes rapidly when exposed to sources of free radicals. It is widely used as a reactive diluent and polymer building block in the formulation of overprint varnishes, inks and a variety of wood, plastic and metal coatings. TMPTA has been tested in a range of in vitro and in vivo genotoxicity tests. There is no clear evidence of induction of gene mutations by TMPTA in bacteria or mammalian cells in vitro, but there is evidence of clastogenicity from induction of small colony tk mutants in the mouse lymphoma assay, and also induction of micronuclei and chromosomal aberrations...
April 2018: Mutation Research
Sumee Khanal, Priyanka Singh, Svetlana L Avlasevich, Dorothea K Torous, Jeffrey C Bemis, Stephen D Dertinger
Regulatory guidance documents stress the value of assessing multiple tissues and the most appropriate endpoints when evaluating chemicals for in vivo genotoxic potential. However, conducting several independent studies to consider multiple endpoints and/or tissue compartments is resource intensive. Furthermore, conventional approaches for scoring genotoxicity endpoints are slow, tedious, and less objective than what would be considered ideal. In an effort to address these issues with current practices, we attempted to i) employ flow cytometry-based methods to score liver micronuclei, blood micronuclei, and blood Pig-a gene mutation, and ii) integrate the endpoints into a common general toxicology study design-the rat 28-day repeat dose study...
April 2018: Mutation Research
Karuppasamy C V, Ramachandran E N, Anil Kumar V, Vivek Kumar P R, Koya P K M, Jaikrishan G, Birajalaxmi Das
Chromosome aberration analysis was carried out in peripheral blood lymphocytes of adult male individuals from normal level natural radiation areas (NLNRA, ≤1.5 mGy/year, N = 27) and high level natural radiation areas (HLNRA, >1.5mGy/year, N = 70) of Kerala coast in southwest India. The mean age of individuals from NLNRA and HLNRA was 40.9 ± 9.4 and 43.7 ± 12.4 years, respectively, with an overall mean of 42.9 ± 11.6 (range: 18-80). Whole-blood cultures were set up and about 260 metaphases were scored per individual...
April 2018: Mutation Research
Monira M Rageh, Reem H El-Gebaly
The radioprotective and antioxidant activities of melanin nanoparticles (MNP) were investigated in Chinese hamster ovary (CHO) cells in vitro and BALB/C mice in vivo. The endpoints measured were cell viability, superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) levels, DNA damage (comet assay), and histopathological examination of tissues. Irradiated groups showed decreased SOD activity and increased MDA levels. Irradiation caused a 3-10-fold increase in comet parameters such as % tail DNA. Treatment with MNP protected cells from DNA damage and death, restored SOD activity, and decreased MDA production...
April 2018: Mutation Research
Tetsuya Suzuki, Kyomu Matsumoto, Masamitsu Honma, Takehiko Nohmi
In regulatory genetic toxicology, it is an axiom that there is no threshold for genotoxicity of chemicals, such that genotoxic chemicals may impose carcinogenic risk on humans even at very low doses. This paradigm is counterintuitive, however, because humans possess a number of self-defense mechanisms that may suppress the genotoxicity at these low doses and therefore manifest a practical threshold. DNA polymerase zeta (Pol ζ) is a specialized Pol that plays an important role in DNA synthesis across DNA damage, thereby modulating cell survival and genotoxicity...
April 2018: Mutation Research
Priya Goswami, Subhabrata Paul, Ritesh Banerjee, Rita Kundu, Anita Mukherjee
Betulinic acid (BA) is a naturally occurring terpenoid found principally in the bark of birch trees as well as in numerous other plants. BA is reported to inhibit cancer progression and induce apoptosis in multiple tumor types. In the present study we have investigated the cytotoxicity and potential genotoxicity of BA in SiHa cells. The cell viability was measured by using MTT assay and the morphological changes, DNA damage, changes in cell cycle and mitochondrial membrane potential (MMP) were used for the assessment of apoptosis...
April 2018: Mutation Research
Sasikumar Muthusamy, Cheng Peng, Jack C Ng
Some polyaromatic hydrocarbons (PAHs) and metals are known human carcinogens and the combined toxicity data of these co-contaminants are important for assessing their health risk. In this study, we have evaluated the combined genotoxicity, AhR activity and cell cycle parameters of four PAHs (benzo[a]pyrene (Ba]P), naphthalene (Nap), phenanthrene (Phe) and pyrene (Pyr)) and three metals (arsenic (As), cadmium (Cd), and lead (Pb)) in HepG2 cells using a flow cytometry based micronucleus (MN) test CAFLUX assay and nuclear fluorescence assay, respectively...
March 2018: Mutation Research
Junko Kajimura, Seishi Kyoizumi, Yoshiko Kubo, Munechika Misumi, Kengo Yoshida, Tomonori Hayashi, Kazue Imai, Waka Ohishi, Kei Nakachi, Nan-Ping Weng, Lauren F Young, Jae-Hung Shieh, Malcolm A Moore, Marcel R M van den Brink, Yoichiro Kusunoki
No abstract text is available yet for this article.
March 2018: Mutation Research
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