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Mutation Research

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https://www.readbyqxmd.com/read/28704682/mutagenic-potential-of-hypoxanthine-in-live-human-cells
#1
Stephen DeVito, Jordan Woodrick, Linze Song, Rabindra Roy
Hypoxanthine (Hx) is a major DNA lesion generated by deamination of adenine during chronic inflammatory conditions, which is an underlying cause of various diseases including cancer of colon, liver, pancreas, bladder and stomach. There is evidence that deamination of DNA bases induces mutations, but no study has directly linked Hx accumulation to mutagenesis and strand-specific mutations yet in human cells. Using a site-specific mutagenesis approach, we report the first direct evidence of mutation potential and pattern of Hx in live human cells...
June 28, 2017: Mutation Research
https://www.readbyqxmd.com/read/28693746/so-similar-yet-so-different-the-two-ends-of-a-double-strand-break
#2
REVIEW
Keun P Kim, Ekaterina V Mirkin
Homologous recombination (HR) is essential for ensuring proper segregation of chromosomes in the first round of meiotic division. HR is also crucial for preserving genomic integrity of somatic cells due to its ability to rescue collapsed replication forks and eliminate deleterious DNA lesions, such as double-strand breaks (DSBs), interstrand crosslinks, and single-strand DNA gaps. Here, we review the early steps of HR (homology search and strand exchange), focusing on the roles of the two ends of a DSB. A detailed overview of the basic HR machinery and its mechanism for template selection and capture of duplex DNA via strand exchange is provided...
June 27, 2017: Mutation Research
https://www.readbyqxmd.com/read/28689138/enhanced-dna-double-strand-break-repair-of-microbeam-targeted-a549-lung-carcinoma-cells-by-adjacent-wi38-normal-lung-fibroblast-cells-via-bi-directional-signaling
#3
Alisa Kobayashi, Tengku Ahbrizal Farizal Tengku Ahmad, Narongchai Autsavapromporn, Masakazu Oikawa, Shino Homma-Takeda, Yoshiya Furusawa, Jun Wang, Teruaki Konishi
Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively...
June 23, 2017: Mutation Research
https://www.readbyqxmd.com/read/28666590/regulation-of-dna-damage-tolerance-in-mammalian-cells-by-post-translational-modifications-of-pcna
#4
REVIEW
Rie Kanao, Chikahide Masutani
DNA damage tolerance pathways, which include translesion DNA synthesis (TLS) and template switching, are crucial for prevention of DNA replication arrest and maintenance of genomic stability. However, these pathways utilize error-prone DNA polymerases or template exchange between sister DNA strands, and consequently have the potential to induce mutations or chromosomal rearrangements. Post-translational modifications of proliferating cell nuclear antigen (PCNA) play important roles in controlling these pathways...
June 21, 2017: Mutation Research
https://www.readbyqxmd.com/read/28641889/mut-res-special-section-protein-modifications-in-dna-repair-and-cancer
#5
EDITORIAL
Minoru Takata
No abstract text is available yet for this article.
June 15, 2017: Mutation Research
https://www.readbyqxmd.com/read/28625404/editorial
#6
REVIEW
Minoru Takata
No abstract text is available yet for this article.
June 10, 2017: Mutation Research
https://www.readbyqxmd.com/read/28646746/variable-spontaneous-mutation-rate-in-clinical-strains-of-multidrug-resistant-acinetobacter-baumannii-and-differentially-expressed-proteins-in-a-hypermutator-strain
#7
Morteza Karami-Zarandi, Masoumeh Douraghi, Behrouz Vaziri, Habibeh Adibhesami, Mohammad Rahbar, Mehdi Yaseri
BACKGROUND: The emergence of multidrug resistant Acinetobacter baumannii within hospitals poses a significant threat to patients. The inherent rate of mutation of these strains has not been described nor has the mechanism by which drug resistance arises. METHODS: Here, we determined the spontaneous mutation rates in 93 clinical strains of A. baumannii using fluctuation analysis. To rule out the clonal relatedness of hypermutator strains, pulsed-field gel electrophoresis (PFGE) was conducted...
June 8, 2017: Mutation Research
https://www.readbyqxmd.com/read/28552167/eukaryotic-dna-damage-responses-homologous-recombination-factors-and-ubiquitin-modification
#8
REVIEW
Nam Soo Lee, Soomi Kim, Yong Woo Jung, Hongtae Kim
To prevent genomic instability disorders, cells have developed a DNA damage response. The response involves various proteins that sense damaged DNA, transduce damage signals, and effect DNA repair. In addition, ubiquitin modifications modulate the signaling pathway depending on cellular context. Among various types of DNA damage, double-stranded breaks are highly toxic to genomic integrity. Homologous recombination (HR) repair is an essential mechanism that fixes DNA damage because of its high level of accuracy...
May 6, 2017: Mutation Research
https://www.readbyqxmd.com/read/28552166/activation-of-the-fa-pathway-mediated-by-phosphorylation-and-ubiquitination
#9
REVIEW
Masamichi Ishiai, Koichi Sato, Junya Tomida, Hiroyuki Kitao, Hitoshi Kurumizaka, Minoru Takata
Fanconi anemia (FA) is a devastating hereditary condition that impacts genome integrity, leading to clinical features such as skeletal and visceral organ malformations, attrition of bone marrow stem cells, and carcinogenesis. At least 21 proteins, when absent or defective, have been implicated in this disorder, and they together constitute the FA pathway, which functions in detection and repair of, and tolerance to, endogenous DNA damage. The damage primarily handled by the FA pathway has been assumed to be related to DNA interstrand crosslinks (ICLs)...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#10
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28501645/targeted-sequencing-identifies-novel-variants-involved-in-autosomal-recessive-hereditary-hearing-loss-in-qatari-families
#11
Moza K Alkowari, Diego Vozzi, Shruti Bhagat, Navaneethakrishnan Krishnamoorthy, Anna Morgan, Yousra Hayder, Barathy Logendra, Nehal Najjar, Ilaria Gandin, Paolo Gasparini, Ramin Badii, Giorgia Girotto, Khalid Abdulhadi
Hereditary hearing loss is characterized by a very high genetic heterogeneity. In the Qatari population the role of GJB2, the worldwide HHL major player, seems to be quite limited compared to Caucasian populations. In this study we analysed 18 Qatari families affected by non-syndromic hearing loss using a targeted sequencing approach that allowed us to analyse 81 genes simultaneously. Thanks to this approach, 50% of these families (9 out of 18) resulted positive for the presence of likely causative alleles in 6 different genes: CDH23, MYO6, GJB6, OTOF, TMC1 and OTOA...
May 4, 2017: Mutation Research
https://www.readbyqxmd.com/read/28501329/eukaryotic-dna-replication-orchestrated-action-of-multi-subunit-protein-complexes
#12
REVIEW
Sukhyun Kang, Mi-Sun Kang, Eunjin Ryu, Kyungjae Myung
Genome duplication is an essential process to preserve genetic information between generations. The eukaryotic cell cycle is composed of functionally distinct phases: G1, S, G2, and M. One of the key replicative proteins that participate at every stage of DNA replication is the Mcm2-7 complex, a replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on the replication origins by replication-initiator proteins, ORC and Cdc6. Two kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an active helicase, the CMG complex in the S phase...
May 1, 2017: Mutation Research
https://www.readbyqxmd.com/read/28676266/frequencies-of-micronucleated-reticulocytes-a-dosimeter-of-dna-double-strand-breaks-in-infants-receiving-computed-tomography-or-cardiac-catheterization
#13
Mona Khattab, Dale M Walker, Richard J Albertini, Janice A Nicklas, Lennart K A Lundblad, Pamela M Vacek, Vernon E Walker
The use of computed tomography (CT scans) has increased dramatically in recent decades, raising questions about the long-term safety of CT-emitted x-rays especially in infants who are more sensitive to radiation-induced effects. Cancer risk estimates for CT scans typically are extrapolated from models; therefore, new approaches measuring actual DNA damage are needed for improved estimations. Hence, changes in a dosimeter of DNA double-strand breaks, micronucleated reticulocytes (MN-RETs) measured by flow cytometry, were investigated in mice and infants exposed to CT scans...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676265/ultrafine-particles-ufps-from-domestic-wood-stoves-genotoxicity-in-human-lung-carcinoma-a549-cells
#14
Marabini Laura, Ozgen Senem, Turacchi Silvia, Aminti Stefania, Arnaboldi Francesca, Lonati Giovanni, Fermo Paola, Corbella Lorenza, Valli Gianluigi, Bernardoni Vera, Dell'Acqua Manuela, Vecchi Roberta, Becagli Silvia, Caruso Donatella, Corrado L Galli, Marinovich Marina
In this paper, results on the potential toxicity of ultrafine particles (UFPs d<100nm) emitted by the combustion of logwood and pellet (hardwood and softwood) are reported. The data were collected during the TOBICUP (TOxicity of BIomass COmbustion generated Ultrafine Particles) project, carried out by a team composed of interdisciplinary research groups. The genotoxic evaluation was performed on A549 cells (human lung carcinomacells) using UFPs whose chemical composition was assessed by a suite of analytical techniques...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676264/in-vivo-genotoxicity-evaluation-of-efavirenz-efv-and-tenofovir-disoproxil-fumarate-tdf-alone-and-in-their-clinical-combinations-in-drosophila-melanogaster
#15
Aroldo Vieira de Moraes Filho, Cláudia de Jesus Silva Carvalho, Cícero Jorge Verçosa, Macks Wendhell Gonçalves, Cláudia Rohde, Daniela de Melo E Silva, Kênya Silva Cunha, Lee Chen-Chen
This study focuses on the antiretrovirals efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and tenofovir disoproxil fumarate (TDF), an oral prodrug of tenofovir analog of adenosine 5'-monophosphate, which belongs to the class of nucleotide reverse transcriptase inhibitors. Both compounds act on the mechanisms of HIV replication, inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. The toxic and genotoxic potential of EFV and TDF alone and in combinations {EFV+combivir [zidovudine (AZT)+lamivudine (3TC)] and TDF+3TC} were assessed using the comet assay and the somatic mutation and recombination test (SMART) in Drosophila melanogaster...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676263/slight-hypercalcemia-is-not-associated-with-positive-responses-in-the-comet-assay-in-male-rat-liver
#16
Anette Thiel, Annie Hamel, Katrien Schaefer, Renato Cardoso, Paul Beilstein
Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676262/adaptive-response-in-mouse-bone-marrow-stromal-cells-exposed-to-900mhz-radiofrequency-fields-impact-of-poly-adp-ribose-polymerase-parp
#17
Qina He, Lin Zong, Yulong Sun, Vijayalaxmi, Thomas J Prihoda, Jian Tong, Yi Cao
This study examined whether non-ionizing radiofrequency fields (RF) exposure is capable of inducing poly (ADP-ribose) polymerase-1 (PARP-1) in bone marrow stromal cells (BMSCs) and whether it plays a role in RF-induced adaptive response (AR). Bone marrow stromal cells (BMSCs) were exposed to 900MHz RF at 120μW/cm(2) power flux density for 3h/day for 5days and then challenged with a genotoxic dose of 1.5Gy gamma-radiation (GR). Some cells were also treated with 3-aminobenzamide (3-AB, 2mM final concentration), a potent inhibitor of PARP-1...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676261/an-assay-to-detect-dna-damaging-agents-that-induce-nucleotide-excision-repairable-dna-lesions-in-living-human-cells
#18
Reine Takatsuka, Shunsuke Ito, Shigenori Iwai, Isao Kuraoka
Biochemical risk assessment studies of chemicals that induce DNA lesions are important, because lesions in genomic DNA frequently result in cancer, neurodegeneration, and aging in humans. Many classes of DNA lesions induced by chemical agents are eliminated via DNA repair mechanisms, such as nucleotide excision repair (NER) and base excision repair (BER), for the maintenance of genomic integrity. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28622829/investigation-of-j-shaped-dose-responses-induced-by-exposure-to-the-alkylating-agent-n-methyl-n-nitrosourea
#19
Katherine E Chapman, George R Hoffmann, Shareen H Doak, Gareth J S Jenkins
Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28622828/the-index-of-ideality-of-correlation-a-criterion-of-predictive-potential-of-qspr-qsar-models
#20
Andrey A Toropov, Alla P Toropova
The index of ideality of correlation (IIC) is a new criterion of the predictive potential of quantitative structure-property/activity relationships (QSPRs/QSARs). This IIC is calculated with using of the correlation coefficient between experimental and calculated values of endpoint for the calibration set, with taking into account the positive and negative dispersions between experimental and calculated values. The mutagenicity is well-known important characteristic of substances from ecological point of view...
July 2017: Mutation Research
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