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Blake R Rushing, Mustafa I Selim
Aflatoxin B1 (AFB1), a class 1 carcinogen and prominent food contaminant, is highly linked to the development of hepatocellular carcinoma (HCC) and plays a causative role in a large portion of global HCC cases. We have demonstrated that a mixture of common organic acids (citric and phosphoric acid) along with arginine can eliminate >99% of AFB1 in solution as well as on corn kernels and convert it to the AFB2a-Arg adduct, acting as a potential detoxification process for contaminated foods. Evaluation of toxicokinetic changes after AFB2a-Arg formation show that the product is highly stable in biological fluids, is not metabolized by P450 enzymes, is highly plasma protein bound, has low lipid solubility, and has poor intestinal permeability/high intestinal efflux compared to AFB1...
January 12, 2018: Oncotarget
Jung-Kuei Chen, Wen-Ling Lin, Zhang Chen, Hung-Wen Liu
Maintenance of genome integrity is critical for both faithful propagation of genetic information and prevention of mutagenesis induced by various DNA damage events. Here we report cold-inducible RNA-binding protein (CIRBP) as a newly identified key regulator in DNA double-strand break (DSB) repair. On DNA damage, CIRBP temporarily accumulates at the damaged regions and is poly(ADP ribosyl)ated by poly(ADP ribose) polymerase-1 (PARP-1). Its dissociation from the sites of damage may depend on its phosphorylation status as mediated by phosphatidylinositol 3-kinase-related kinases...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shuo Yang, Yong Liao, Qi Zhao, Yuqin Xie, Ai Zheng, Huajing Wan
The mitotic spindle, assembled by microtubule organization center (MTOC), is a critical structure required for proper chromosome segregation during mitosis. Studies demonstrated that defects of mitotic spindle assembling would result in chromosome instability, associating with oncogenesis. In this study, we identified that heparanase (HPSE) was localized on MTOC in mitotic cells. Induced expression of HPSE in human airway epithelial cells promoted mitotic spindle formation, and silencing of HPSE expression disrupted the mitotic spindle formation, resulting in chromosome instability, including chromosome mis-segregation and increased micronuclei formation...
February 12, 2018: DNA and Cell Biology
Andrew B Fielding, Matthew Concannon, Sarah Darling, Emma V Rusilowicz-Jones, Joseph J Sacco, Ian A Prior, Michael J Clague, Sylvie Urbé, Judy M Coulson
Ubiquitin-specific protease 15 (USP15) is a widely expressed deubiquitylase that has been implicated in diverse cellular processes in cancer. Here we identify topoisomerase II (TOP2A) as a novel protein that is regulated by USP15. TOP2A accumulates during G2 and functions to decatenate intertwined sister chromatids at prophase, ensuring the replicated genome can be accurately divided into daughter cells at anaphase. We show that USP15 is required for TOP2A accumulation, and that USP15 depletion leads to the formation of anaphase chromosome bridges...
February 12, 2018: Oncogene
Tássia F D Castro, Isadora M Paiva, Aline F S Carvalho, Isadora L Assis, Marcel J Palmieri, Larissa F Andrade-Vieira, Silvana Marcussi, Luis D Solis-Murgas
Spent pot liner (SPL) is a solid waste generated during the primary smelting of aluminum, and its toxicity is attributed to the presence of fluoride, cyanide, and aluminum salts, which can be leached into aquatic ecosystems. Since the effects of this waste on aquatic life forms have not yet been investigated, the objective of our study was to evaluate the toxicity of simulated leachates of SPL on zebrafish (Danio rerio). Animals were exposed to 0 (control), 0.32, 0.64, or 0.95 g L-1 of SPL for 24, 72, and 96 h, and genotoxicity was accessed through micronucleus and comet assays...
February 9, 2018: Environmental Science and Pollution Research International
Minkyoung Lee, Ik Soo Kim, Koog Chan Park, Jong-Seo Kim, Sung Hee Baek, Keun Il Kim
Mis18α, a component of Mis18 complex comprising of Mis18α, Mis18β, and M18BP1, is known to localize at the centromere from late telophase to early G1 phase and plays a priming role in CENP-A deposition. Although its role in CENP-A deposition is well established, the other function of Mis18α remains unknown. Here, we elucidate a new function of Mis18α that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. We find that Aurora B kinase phosphorylates Mis18α during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A...
January 5, 2018: Oncotarget
Geralda Gillian Silva-Sena, Maressa Malini, Juliana Macedo Delarmelina, Jean Carlos Vencioneck Dutra, Suiany Vitorino Gervásio, Marcos André Soares Leal, Thiago de Melo Costa Pereira, Aneli M Barbosa-Dekker, Robert F H Dekker, Flavia de Paula, Maria do Carmo Pimentel Batitucci
The antimutagenic effect of botryosphaeran, an exocellular (1 → 3)(1 → 6)-β-d-glucan, from the ascomyceteous and plant-borne endophytic fungus, Botryosphaeria rhodina MAMB-05, was evaluated in young (6-8 weeks) and elderly (18 months) Swiss albino mice of both genders. The hypolipidemic, hypoglycemic and antiatherogenic potential was also evaluated in 18-month old male LDL receptor knockout (LDLr-/-) mice. Administration of botryosphaeran by gavage (doses: 7.5, 15, 30 mg/kg b.w./day) in a 30-day pretreatment protocol (young mice), or 15-day protocol (older mice), did not cause genotoxicity as assessed by the micronucleus test in peripheral blood (PB) and bone marrow cells (BMCs)...
February 2018: Mutation Research
Jorge Castro-Garza, Miriam Lorena Luévano-Martínez, Licet Villarreal-Treviño, Jaime Gosálvez, José Luis Fernández, Martha Imelda Dávila-Rodríguez, Catalina García-Vielma, Silvia González-Hernández, Elva Irene Cortés-Gutiérrez
BACKGROUND: Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes. OBJECTIVES: To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages. METHODS: We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe...
March 2018: Memórias do Instituto Oswaldo Cruz
Gang Li, Pan Yang, Shuai Hao, Wei Hu, Cheng Liang, Bing-Shuang Zou, Xu-Chen Ma
The aim of the present study was to monitor genotoxic and cytotoxic effect of X-ray on exfoliated buccal mucosa cells and investigate the association between the effects and the accumulated absorbed doses of oral mucosa. 98 participants' buccal mucosa cells were collected before and 10 days after different series of dental radiographs performed. Cytological preparations were successively dyed with the methods of Feulgen and fast-green, and analyzed under a light microscope. Micronuclei (MN)and other cells were scored...
February 6, 2018: Scientific Reports
Raissa Borges Ishikawa, Juliana Miron Vani, Silvia Cordeiro das Neves, Ana Paula Maluf Rabacow, Cândida Aparecida Leite Kassuya, Júlio Croda, Claudia Andrea Lima Cardoso, Antônio Carlos Duenhas Ferreira Monreal, Andreia Conceição Milan Brochado Antoniolli, Andréa Luiza Cunha-Laura, Rodrigo Juliano Oliveira
ETHNOPHARMACOLOGICAL RELEVANCE: Doliocarpus dentatus (Dilleniaceae) is commonly used in Brazil for the treatment of inflammatory process pain and urinary retention. Previous studies of our group have demonstrated the anti-inflammatory and antimycobacterial action of the ethanolic extract of Doliocarpus dentatus (EEDd) as well as the safety of its use. AIM OF THE STUDY: we investigated the effects of EEDd on reproductive performance, fetal development and DNA integrity in pregnant female Swiss mice...
January 30, 2018: Journal of Ethnopharmacology
Srinivas Chinde, Y Poornachandra, Archana Panyala, Srinivas Indu Kumari, Suresh Yerramsetty, Harikrishna Adicherla, Paramjit Grover
The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO3 NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO3 NPs and their microparticles (MPs) using different concentrations (0-300 μg ml-1 ) in human lung carcinoma (A549) cells. The mean size of WO3 NPs and MPs by transmission electron microscopy was 53.84 nm and 3.88 μm, respectively...
February 6, 2018: Journal of Applied Toxicology: JAT
Preeti Bagri, S K Jain
Acetamiprid (ACE), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations (CA) assay was utilized to assess the genotoxic effects of ACE in bone marrow of Swiss albino male mice. Acetamiprid was administered i.p. daily at 4.6 and 2.3 mg/kg/day along with 3% gum acacia as negative control for 60 and 90 days and cyclophosphamide (50 mg/kg b.wt.) as positive control...
February 6, 2018: Drug and Chemical Toxicology
Mary T Sylvia, Lavanya Baskaran, Ramachandra V Bhat
Background: Micronucleus is a small fragment of nucleus present in the cells which have undergone chromosomal damage. It is used as a biomarker of genomic damage. Aims: We aim to study the presence of micronucleus on breast cytology smears and the use of scoring the micronucleus as an additional criteria for the classification of breast lesions with emphasis on borderline gray zone categories. Settings and Design: This is a cross-sectional retrospective descriptive study...
January 2018: Journal of Cytology
T V N Ratna Kumari, B R Ahmed Mujib
Objectives: One percent toluidine blue being the most effective adjunct is often used to detect dysplasia. Not much attention has been given to the effect of toluidine blue in enhancement of cytological smears. The present study assessed the smears before and after application of toluidine blue in smokers against non-smokers using three different stains [Papanicolaou (PAP), Hematoxylin and Eosin (H and E), and Giemsa]. Study Design: Twenty-five individuals from each group participated in the study...
January 2018: Journal of Cytology
Fengchao Li, Yanbo Li, Dan Luo, Miao Miao, Chen Shao
The morphology and morphogenesis of a new soil hypotrich ciliate, Sterkiella multicirrata sp. nov., was investigated using live observation and protargol staining. The new species is characterised by: body elliptical, 110-180 × 45-75 μm in vivo, an average of 35 adoral membranelles; usually 19 frontoventral-transverse cirri, consisting of three frontal, five frontoventral, one buccal, four postoral ventral, two pretransverse, and four transverse cirri; four macronuclear nodules, and two to five micronuclei...
February 3, 2018: Journal of Eukaryotic Microbiology
Aneela Jamil, Amir Rashid, Abdul Khaliq Naveed, Asifa Majeed
OBJECTIVE: To investigate the relation between serum amyloid A-low density lipoprotein (SAA-LDL) and genotoxicity in smokers. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Army Medical College, Rawalpindi and National Institute of Health (NIH), Islamabad, from June 2014 to February 2015. METHODOLOGY: Seventy healthy Sprague Dawley rats were purchased from NIH and exposed to cigarette smoke in smoke chamber for three months...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Katsuya Yamamoto, Shinichiro Kawamoto, Keiji Kurata, Akihito Kitao, Yu Mizutani, Hiroya Ichikawa, Kimikazu Yakushijin, Kazuyoshi Kajimoto, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami
Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11...
January 24, 2018: Cytogenetic and Genome Research
Arup Ranjan Patra, Somnath Singha Roy, Abhishek Basu, Avishek Bhuniya, Arin Bhattacharjee, Subhadip Hajra, Ugir Hossain Sk, Rathindranath Baral, Sudin Bhattacharya
A newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b.wt, i.p. for 10 days) in female Swiss albino mouse. MUS treatment reduced (P < 0.001) the percentage of chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in murine bone marrow cells and also enhanced (P < 0...
February 1, 2018: Scientific Reports
Xiaoqing Guo, Ji-Eun Seo, Steven M Bryce, Jenna A Tan, Qiangen Wu, Stacey L Dial, M Moore Martha, Nan Mei
TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In the present study, we investigated and quantified the genotoxicity of four structurally similar nitroxides, TEMPO and three of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Julia Harris Behnfeldt, Samir Acharya, Larissa Tangeman, April Sandy Gocha, Jeremy Keirsey, Joanna Groden
The recQ-like helicase BLM interacts directly with topoisomerase IIα to regulate chromosome breakage in human cells. We demonstrate that a phosphosite tri-serine cluster (S577/S579/S580) within the BLM topoisomerase IIα-interaction region is required for this function. Enzymatic activities of BLM and topoisomerase IIα are reciprocally stimulated in vitro by ten-fold for topoisomerase IIα decatenation/relaxation activity and three-fold for BLM unwinding of forked DNA duplex substrates. A BLM transgene encoding alanine substitutions of the tri-serine cluster in BLM-/- transfected cells increases micronuclei, DNA double strand breaks and anaphase ultrafine bridges (UFBs), and decreases cellular co-localization of BLM with topoisomerase IIα...
January 27, 2018: Human Molecular Genetics
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