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Toxicogenomics

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https://www.readbyqxmd.com/read/27928627/recommended-approaches-in-the-application-of-toxicogenomics-to-derive-points-of-departure-for-chemical-risk-assessment
#1
Reza Farmahin, Andrew Williams, Byron Kuo, Nikolai L Chepelev, Russell S Thomas, Tara S Barton-Maclaren, Ivan H Curran, Andy Nong, Michael G Wade, Carole L Yauk
There is increasing interest in the use of quantitative transcriptomic data to determine benchmark dose (BMD) and estimate a point of departure (POD) for human health risk assessment. Although studies have shown that transcriptional PODs correlate with those derived from apical endpoint changes, there is no consensus on the process used to derive a transcriptional POD. Specifically, the subsets of informative genes that produce BMDs that best approximate the doses at which adverse apical effects occur have not been defined...
December 7, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27909446/functional-toxicogenomic-profiling-expands-insight-into-modulators-of-formaldehyde-toxicity-in-yeast
#2
Matthew North, Brandon D Gaytán, Carlos Romero, Vanessa Y De La Rosa, Alex Loguinov, Martyn T Smith, Luoping Zhang, Chris D Vulpe
Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27905518/pesticide-toxicogenomics-across-scales-in-vitro-transcriptome-predicts-mechanisms-and-outcomes-of-exposure-in-vivo
#3
Immacolata Porreca, Fulvio D'Angelo, Lucia De Franceschi, Alessandro Mattè, Michele Ceccarelli, Achille Iolascon, Alberto Zamò, Filomena Russo, Maria Ravo, Roberta Tarallo, Marzia Scarfò, Alessandro Weisz, Mario De Felice, Massimo Mallardo, Concetta Ambrosino
In vitro Omics analysis (i.e. transcriptome) is suggested to predict in vivo toxicity and adverse effects in humans, although the causal link between high-throughput data and effects in vivo is not easily established. Indeed, the chemical-organism interaction can involve processes, such as adaptation, not established in cell cultures. Starting from this consideration we investigate the transcriptomic response of immortalized thyrocytes to ethylenthiourea and chlorpyrifos. In vitro data revealed specific and common genes/mechanisms of toxicity, controlling the proliferation/survival of the thyrocytes and unrelated hematopoietic cell lineages...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864593/toxicogenomics-in-environmental-science
#4
Alexandra Brinke, Sebastian Buchinger
This chapter reviews the current knowledge and recent progress in the field of environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods. In ecotoxicogenomics the omics technologies are applied for the detection and assessment of adverse effects in the environment, and thus are to be distinguished from omics used in human toxicology [Snape et al., Aquat Toxicol 67:143-154, 2004]. Transcriptomic methods in ecotoxicology are applied to gain a mechanistic understanding of toxic effects on organisms or populations, and thus aim to bridge the gap between cause and effect...
November 19, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27855314/alterations-of-gene-expression-indicating-effects-on-estrogen-signaling-and-lipid-homeostasis-in-seabream-hepatocytes-exposed-to-extracts-of-seawater-sampled-from-a-coastal-area-of-the-central-adriatic-sea-italy
#5
Paolo Cocci, Martina Capriotti, Gilberto Mosconi, Alessandra Campanelli, Emanuela Frapiccini, Mauro Marini, Giovanni Caprioli, Gianni Sagratini, Graziano Aretusi, Francesco Alessandro Palermo
Recent evidences suggest that the toxicological effects of endocrine disrupting chemicals (EDCs) involve multiple nuclear receptor-mediated pathways, including estrogen receptor (ER) and peroxisome proliferator-activated receptor (PPAR) signaling systems. Thus, our objective in this study was to detect the summated endocrine effects of EDCs with metabolic activity in coastal waters of the central Adriatic Sea by means of a toxicogenomic approach using seabream hepatocytes. Gene expression patterns were also correlated with seawater levels of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs)...
November 2, 2016: Marine Environmental Research
https://www.readbyqxmd.com/read/27827897/comparative-analysis-of-toxic-responses-of-organic-extracts-from-diesel-and-selected-alternative-fuels-engine-emissions-in-human-lung-beas-2b-cells
#6
Helena Libalova, Pavel Rossner, Kristyna Vrbova, Tana Brzicova, Jitka Sikorova, Michal Vojtisek-Lom, Vit Beranek, Jiri Klema, Miroslav Ciganek, Jiri Neca, Katerina Pencikova, Miroslav Machala, Jan Topinka
This study used toxicogenomics to identify the complex biological response of human lung BEAS-2B cells treated with organic components of particulate matter in the exhaust of a diesel engine. First, we characterized particles from standard diesel (B0), biodiesel (methylesters of rapeseed oil) in its neat form (B100) and 30% by volume blend with diesel fuel (B30), and neat hydrotreated vegetable oil (NEXBTL100). The concentration of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in organic extracts was the lowest for NEXBTL100 and higher for biodiesel...
November 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821072/de-novo-assembly-and-analysis-of-changes-in-the-protein-coding-transcriptome-of-the-freshwater-shrimp-paratya-australiensis-decapoda-atyidae-in-response-to-acid-sulfate-drainage-water
#7
Peter A Bain, Adrienne L Gregg, Anupama Kumar
BACKGROUND: The atyid shrimp Paratya australiensis occurs in surface freshwater habitats throughout eastern Australia and has been used to study the ecotoxicology of contaminants such as pesticides and metals. The acidification of surface water that can occur after acid sulfate material in soils and sediments is oxidised and subsequently re-wetted is a serious environmental issue in coastal regions and inland riverine floodplains worldwide. Solubilisation of soil-associated minerals can result in high waterborne concentrations of mineral salts and dissolved metals, which together with low pH represent a potential threat to aquatic ecosystems in affected regions...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27818731/prediction-of-non-genotoxic-carcinogenicity-based-on-genetic-profiles-of-short-term-exposure-assays
#8
Luis Orlando Pérez, Rolando González-José, Pilar Peral García
Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals...
October 2016: Toxicological Research
https://www.readbyqxmd.com/read/27810435/candidate-methylated-genes-in-osteoarthritis-explored-by-bioinformatics-analysis
#9
Jie Liu, Yangquan Hao, Yugui Wang, Shouye Hu, Ke Xu, Chao Lu
BACKGROUND: This study aimed to explore potential novel genes correlated with osteoarthritis (OA). METHODS: The gene expression profile of GSE48422 was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included five arthritic cartilage samples and five non-arthritic cartilage samples from five female OA patients. Differentially methylated genes (DMGs) between the two kinds of samples were identified, followed by their functional analysis and protein-protein interaction (PPI) analysis...
December 2016: Knee
https://www.readbyqxmd.com/read/27776381/molecular-targets-of-developmental-exposure-to-bisphenol-a-in-diabesity-a-focus-on-endoderm-derived-organs
#10
REVIEW
I Porreca, L Ulloa-Severino, P Almeida, D Cuomo, A Nardone, G Falco, M Mallardo, C Ambrosino
Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure...
January 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27766956/application-of-dynamic-topic-models-to-toxicogenomics-data
#11
Mikyung Lee, Zhichao Liu, Ruili Huang, Weida Tong
BACKGROUND: All biological processes are inherently dynamic. Biological systems evolve transiently or sustainably according to sequential time points after perturbation by environment insults, drugs and chemicals. Investigating the temporal behavior of molecular events has been an important subject to understand the underlying mechanisms governing the biological system in response to, such as, drug treatment. The intrinsic complexity of time series data requires appropriate computational algorithms for data interpretation...
October 6, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27761495/gene-expression-data-from-acetaminophen-induced-toxicity-in-human-hepatic-in-vitro-systems-and-clinical-liver-samples
#12
Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
https://www.readbyqxmd.com/read/27760801/toxicogenomics-analysis-of-mouse-lung-responses-following-exposure-to-titanium-dioxide-nanomaterials-reveal-their-disease-potential-at-high-doses
#13
Luna Rahman, Dongmei Wu, Michael Johnston, Andrew William, Sabina Halappanavar
Titanium dioxide nanoparticles (TiO2NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO2NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO2NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO2NPs...
October 19, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27749045/toxicogenomic-assessment-of-6-oh-bde47-induced-developmental-toxicity-in-chicken-embryo
#14
Ying Peng, Pu Xia, Junjiang Zhang, Daniel L Villeneuve, Jiamin Zhang, Zhihao Wang, Si Wei, Hongxia Yu, Xiaowei Zhang
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are analogs of PBDEs with hundreds of possible structures and are frequently detected in the environment. However, the in vivo evidence on the toxicity of OH-PBDEs is still very limited. Here the developmental toxicity of 6-OH-BDE47, a predominant congener of OH-PBDEs detected in the environment, in chicken embryos was assessed using a toxicogenomic approach. Fertilized chicken eggs were dosed via in ovo administration of 0.006 to 0.474 nmol 6-OH-BDE47/g egg followed by 18-days incubation...
October 17, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/27737797/toxicogenomic-profile-of-apoptotic-and-necrotic-sn56-basal-forebrain-cholinergic-neuronal-loss-after-acute-and-long-term-chlorpyrifos-exposure
#15
Paula Moyano, Javier Del Pino, María José Anadon, María Jesús Díaz, Gloria Gómez, María Teresa Frejo
Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce, both after acute and repeated exposure, learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. This effect was reported to be induced through apoptotic process, partially mediated by AChE overexpression, although neuronal necrosis was also described after CPF exposure...
October 10, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27724849/mining-kidney-toxicogenomic-data-by-using-gene-co-expression-modules
#16
Mohamed Diwan M AbdulHameed, Danielle L Ippolito, Jonathan D Stallings, Anders Wallqvist
BACKGROUND: Acute kidney injury (AKI) caused by drug and toxicant ingestion is a serious clinical condition associated with high mortality rates. We currently lack detailed knowledge of the underlying molecular mechanisms and biological networks associated with AKI. In this study, we carried out gene co-expression analyses using DrugMatrix-a large toxicogenomics database with gene expression data from rats exposed to diverse chemicals-and identified gene modules associated with kidney injury to probe the molecular-level details of this disease...
October 10, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27678064/toxicogenomic-analysis-identifies-the-apoptotic-pathway-as-the-main-cause-of-hepatotoxicity-induced-by-tributyltin
#17
Mi Zhou, Mei Feng, Ling-Ling Fu, Lin-Dan Ji, Jin-Shun Zhao, Jin Xu
Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear...
September 24, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27671623/low-concentrations-of-bromodichloromethane-induce-a-toxicogenomic-response-in-porcine-embryos-in-vitro
#18
Florence Pagé-Larivière, Amélie Tremblay, Céline Campagna, Manuel J Rodriguez, Marc-André Sirard
Bromodichloromethane (BDCM) is one of the trihalomethanes present in chlorinated water. Humans are thus daily exposed. Previous contradictory results failed to clearly establish the adverse effects of low concentrations of BDCM. By using the porcine preimplantation embryo as a sensitive model, we showed that exposure to low concentrations of BDCM (10 and 100ppb) during the first week of embryo development induced adverse effect on the blastocyst rate and alteration of the estradiol pathway. Our results also suggest that blastocysts exposed to BDCM present transcriptomic and epigenomic adaptive modifications compatible with the cardiac anomalies observed by previous studies of newborns exposed to BDCM during gestation...
September 23, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27651457/the-comparative-toxicogenomics-database-update-2017
#19
Allan Peter Davis, Cynthia J Grondin, Robin J Johnson, Daniela Sciaky, Benjamin L King, Roy McMorran, Jolene Wiegers, Thomas C Wiegers, Carolyn J Mattingly
The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules...
September 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27632408/correction-meta-analysis-of-large-scale-toxicogenomic-data-finds-neuronal-regeneration-related-protein-and-cathepsin-d-to-be-novel-biomarkers-of-drug-induced-toxicity
#20
Hyosil Kim, Ju-Hwa Kim, So Youn Kim, Deokyeon Jo, Ho Jun Park, Jihyun Kim, Sungwon Jung, Hyun Seok Kim, KiYoung Lee
[This corrects the article DOI: 10.1371/journal.pone.0136698.].
2016: PloS One
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