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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/29150256/reproductive-effects-linked-to-dna-methylation-in-male-zebrafish-chronically-exposed-to-environmentally-relevant-concentrations-of-di-2-ethylhexyl-phthalate
#1
Yan-Bo Ma, Pan-Pan Jia, Muhammad Junaid, Li Yang, Chun-Jiao Lu, De-Sheng Pei
Di-(2-ethylhexyl) phthalate (DEHP) possesses the potential to interfere with the male reproductive endocrine system in mammals; however, its reproductive toxicity in male zebrafish and associated epigenetic studies have not been explored. In this study, three-month-old male zebrafish were exposed to environmentally relevant concentrations of DEHP (0, 10, 33 and 100 μg/L) for 3 months, and then the impact on the reproduction of males and the underlying mechanism were investigated. Histological testing showed that an exposure concentration of 100 μg/L DEHP significantly inhibited spermatogenesis, with an associated decline in capability to fertilize untreated oocytes...
November 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#2
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#3
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29132323/integrative-microrna-and-mrna-deep-sequencing-expression-profiling-in-endemic-burkitt-lymphoma
#4
Cliff I Oduor, Yasin Kaymaz, Kiprotich Chelimo, Juliana A Otieno, John Michael Ong'echa, Ann M Moormann, Jeffrey A Bailey
BACKGROUND: Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence suggest that abnormal modulation of mRNA transcription via miRNAs might be a significant factor in lymphomagenesis. However, the alterations in these miRNAs and their correlations to their putative mRNA targets have not been extensively studied relative to normal germinal center (GC) B cells...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29128564/epigenetic-mechanisms-of-atm-activation-after-helicobacter-pylori-infection
#5
Juliana Carvalho Santos, Rafael Zuppardo Gambeloni, Aline Tengan Roque, Sebastian Oeck, Marcelo Lima Ribeiro
Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes. Among other risk factors, Helicobacter pylori infection is considered the main driving factor of GC development. H. pylori infection increases DNA damage levels and leads to epigenetic dysregulation, which may favor gastric carcinogenesis. An early step in double strand break repair is the recruitment of (ataxia-telangiectasia mutated serine/threonine kinase (ATM) to the damaged site, where it plays a key role in advancing the DNA damage checkpoint process...
November 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29121865/temporally-distinct-transcriptional-regulation-of-myocyte-dedifferentiation-and-myofiber-growth-during-muscle-regeneration
#6
Ke'ale W Louie, Alfonso Saera-Vila, Phillip E Kish, Justin A Colacino, Alon Kahana
BACKGROUND: Tissue regeneration requires a series of steps, beginning with generation of the necessary cell mass, followed by cell migration into damaged area, and ending with differentiation and integration with surrounding tissues. Temporal regulation of these steps lies at the heart of the regenerative process, yet its basis is not well understood. The ability of zebrafish to dedifferentiate mature "post-mitotic" myocytes into proliferating myoblasts that in turn regenerate lost muscle tissue provides an opportunity to probe the molecular mechanisms of regeneration...
November 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29118760/septic-shock-and-the-aging-process-a-molecular-comparison
#7
Fabiano Pinheiro da Silva, Marcel Cerqueira César Machado
Aging is a continuous process promoted by both intrinsic and extrinsic factors that each trigger a multitude of molecular events. Increasing evidence supports a central role for inflammation in this progression. Here, we discuss how the low-grade chronic inflammation that characterizes aging is tightly interconnected with other important aspects of this process, such as DNA damage, mitochondrial dysfunction, and epigenetic changes. Similarly, inflammation also plays a critical role in many morbid conditions that affect patients who are admitted to Intensive Care...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29112861/long-fiber-carbon-nanotubes-replicate-asbestos-induced-mesothelioma-with-disruption-of-the-tumor-suppressor-gene-cdkn2a-ink4a-arf
#8
Tatyana Chernova, Fiona A Murphy, Sara Galavotti, Xiao-Ming Sun, Ian R Powley, Stefano Grosso, Anja Schinwald, Joaquin Zacarias-Cabeza, Kate M Dudek, David Dinsdale, John Le Quesne, Jonathan Bennett, Apostolos Nakas, Peter Greaves, Craig A Poland, Ken Donaldson, Martin Bushell, Anne E Willis, Marion MacFarlane
Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma...
November 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29109788/decrease-in-lymphoid-specific-helicase-and-5-hydroxymethylcytosine-is-associated-with-metastasis-and-genome-instability
#9
Jiantao Jia, Ying Shi, Ling Chen, Weiwei Lai, Bin Yan, Yiqun Jiang, Desheng Xiao, Sichuan Xi, Ya Cao, Shuang Liu, Yan Cheng, Yongguang Tao
DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined...
2017: Theranostics
https://www.readbyqxmd.com/read/29108743/differentially-dna-methylation-changes-induced-in-vitro-by-traffic-derived-nanoparticulate-matter
#10
Xiaoning Lei, Joshua E Muscat, Bo Zhang, Xuyang Sha, Guangli Xiu
The cytotoxicity, apoptosis, reactive oxygen species (ROS) and DNA damage induced by the commercial diesel exhaust particulate matter (PM) (SRM2975) with concentrations ranging from 0.1μg·mL(-1) to 20μg·mL(-1) were assessed in human umbilical vein endothelial cells (HUVECs) in vitro. An epigenetics-wide investigation of DNA methylation profiles was also performed using a new methylation beadchip (Illumina 850K) to identify the health effects of traffic-derived nanoparticulate matter (nPM) with a concentration of 20μg·mL(-1)...
November 3, 2017: Toxicology
https://www.readbyqxmd.com/read/29106518/prenatal-ethanol-exposure-and-neocortical-development-a-transgenerational-model-of-fasd
#11
Charles W Abbott, David J Rohac, Riley T Bottom, Sahil Patadia, Kelly J Huffman
Fetal Alcohol Spectrum Disorders, or FASD, represent a range of adverse developmental conditions caused by prenatal ethanol exposure (PrEE) from maternal consumption of alcohol. PrEE induces neurobiological damage in the developing brain leading to cognitive-perceptual and behavioral deficits in the offspring. Alcohol-mediated alterations to epigenetic function may underlie PrEE-related brain dysfunction, with these changes potentially carried across generations to unexposed offspring. To determine the transgenerational impact of PrEE on neocortical development, we generated a mouse model of FASD and identified numerous stable phenotypes transmitted via the male germline to the unexposed third generation...
July 6, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29106445/a-potent-hydroxamic-acid-based-small-molecule-inhibitor-a452-preferentially-inhibits-hdac6-activity-and-induces-cytotoxicity-toward-cancer-cells-irrespective-of-p53-status
#12
Hyun-Wook Ryu, Dong-Hee Shin, Dong Hoon Lee, Hye-Rim Won, So Hee Kwon
HDAC6-selective inhibitors are novel epigenetic anticancer agents. However, their precise mechanisms of action are incompletely understood. We investigated the anticancer mechanisms of the novel potent and selective HDAC6 inhibitor A452 compared with current clinically tested HDAC6 inhibitor ACY-1215. We demonstrate that A452 effectively inhibits the cell growth and viability of various cancer cell types, irrespective of p53 status. A452 induced apoptosis as evidenced by activated caspase 3 and PARP, increased Bak and Bax, and decreased Bcl-xL...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29102535/bisphenol-af-negatively-affects-oocyte-maturation-of-mouse-in-vitro-through-increasing-oxidative-stress-and-dna-damage
#13
Zhi-Ming Ding, Xiao-Fei Jiao, Di Wu, Jia-Yu Zhang, Fan Chen, Yong-Sheng Wang, Chun-Jie Huang, Shou-Xin Zhang, Xiang Li, Li-Jun Huo
Bisphenol AF (BPAF) is commonly used in industry production as a substitute for Bisphenol A (BPA). Many studies showed that BPAF negatively affect some physiological processes in humans and animals. However, the effects of BPAF on oocyte maturation and its possible mechanisms are sparsely understood. In the present study, we found that 100 μM BPAF exposure affect oocyte maturation with a decreased first polar body extrusion (PBE) rate. Immunofluorescence study displayed that BPAF exposure disrupt the spindle morphology through affecting the function of microtubule organizing centers (MTOCs), which was confirmed by the dysfunction of γ-tubulin and phosphorylated mitogen-activated protein kinase (p-MAPK)...
November 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29099948/heritable-sperm-chromatin-epigenetics-a-break-to-remember
#14
Ralph G Meyer, Chelsea Ketchum, Mirella L Meyer-Ficca
Sperm chromatin not only has a unique structure to condense and protect the paternal DNA in transit, but also provides epigenetic information that supports embryonic development. Most of the unique sperm nuclear architecture is formed during the sweeping postmeiotic chromatin remodeling events in spermiogenesis, where the majority of nucleosomes are removed and replaced by protamines. The remaining histones and other chromatin proteins are located in structurally and transcriptionally relevant positions in the genome and carry diverse posttranslational modifications relevant to the control of embryonic gene expression...
November 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29082208/dna-damage-in-human-spermatozoa-important-contributor-to-mutagenesis-in-the-offspring
#15
Robert John Aitken
Nuclear DNA damage in spermatozoa could potentially have a major impact on the fertilizing capacity of these cells, their ability to establish a normal pattern of embryonic development as well as the health and wellbeing of subsequent offspring. Many laboratory techniques have been developed to assess this damage focusing on strand breaks, chromatin stability following exposure to extreme pH conditions and the formation of DNA adducts. Of particular importance may be the dominant role played by oxidative stress in the etiology of defective sperm function and DNA damage...
September 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29081695/aging-as-an-epigenetic-phenomenon
#16
REVIEW
Vasily V Ashapkin, Lyudmila I Kutueva, Boris F Vanyushin
INTRODUCTION: Hypermethylation of genes associated with promoter CpG islands, and hypomethylation of CpG poor genes, repeat sequences, transposable elements and intergenic genome sections occur during aging in mammals. Methylation levels of certain CpG sites display strict correlation to age and could be used as "epigenetic clock" to predict biological age. Multi-substrate deacetylases SIRT1 and SIRT6 affect aging via locus-specific modulations of chromatin structure and activity of multiple regulatory proteins involved in aging...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29080344/bile-acids-and-cancer-direct-and-environmental-dependent-effects
#17
Agostino Di Ciaula, David Q-H Wang, Emilio Molina-Molina, Raquel Lunardi Baccetto, Giuseppe Calamita, Vincenzo O Palmieri, Piero Portincasa
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i...
October 28, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29075360/turnover-of-histones-and-histone-variants-in-postnatal-rat-brain-effects-of-alcohol-exposure
#18
Nadia Rachdaoui, Ling Li, Belinda Willard, Takhar Kasumov, Stephen Previs, Dipak Sarkar
BACKGROUND: Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental health problems to poor social adjustment and stress tolerance. Neurons are particularly sensitive to alcohol exposure. The neurotoxic action of alcohol, i.e., through ROS production, induces DNA damage and neuronal cell death by apoptosis...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29074395/epigenetics-of-malignant-melanoma
#19
REVIEW
Bruce Moran, Romina Silva, Antoinette S Perry, William M Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAF(V600E), in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma...
October 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29073177/hypomethylated-fgf3-is-a-potential-biomarker-for-early-detection-of-oral-cancer-in-mice-treated-with-the-tobacco-carcinogen-dibenzo-def-p-chrysene
#20
Yuan-Wan Sun, Kun-Ming Chen, Yuka Imamura Kawasawa, Anna C Salzberg, Timothy K Cooper, Carla Caruso, Cesar Aliaga, Junjia Zhu, Krishne Gowda, Shantu Amin, Karam El-Bayoumy
Genetic and epigenetic alterations observed at end stage OSCC formation could be considered as a consequence of cancer development and thus changes in normal or premalignant tissues which had been exposed to oral carcinogens such as Dibenzo[def,p]chrysene (DBP) may better serve as predictive biomarkers of disease development. Many types of DNA damage can induce epigenetic changes which can occur early and in the absence of evident morphological abnormalities. Therefore we used ERRBS to generate genome-scale, single-base resolution DNA methylomes from histologically normal oral tissues of mice treated with DBP under experimental conditions known to induce maximum DNA damage which is essential for the development of OSCC induced by DBP in mice...
2017: PloS One
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