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Toxicogenomics

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https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#1
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28073477/a-review-of-the-phylogeny-ecology-and-toxin-production-of-bloom-forming-aphanizomenon-spp-and-related-species-within-the-nostocales-cyanobacteria
#2
REVIEW
Samuel Cirés, Andreas Ballot
The traditional genus Aphanizomenon comprises a group of filamentous nitrogen-fixing cyanobacteria of which several memebers are able to develop blooms and to produce toxic metabolites (cyanotoxins), including hepatotoxins (microcystins), neurotoxins (anatoxins and saxitoxins) and cytotoxins (cylindrospermopsin). This genus, representing geographically widespread and extensively studied cyanobacteria, is in fact heterogeneous and composed of at least five phylogenetically distant groups (Aphanizomenon, Anabaena/Aphanizomenon like cluster A, Cuspidothrix, Sphaerospermopsis and Chrysosporum) whose taxonomy is still under revision...
April 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073113/in-vitro-to-in-vivo-extrapolation-for-drug-induced-liver-injury-using-a-pair-ranking-method
#3
Zhichao Liu, Hong Fang, Jürgen Borlak, Ruth Roberts, Weida Tong
Preclinical animal toxicity studies may not accurately predict human toxicity. In light of this, in vitro systems have been developed that have the potential to supplement or even replace animal use. We examined in vitro to in vivo extrapolation (IVIVE) of gene expression data obtained from The Open Japanese Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) for 131 compounds given to rats for 28 days, and to human or rat hepatocytes for 24 hours. Notably, a Pair Ranking (PRank) method was developed to assess IVIVE potential with a PRank score based on the preservation of the order of similarity rankings of compound pairs between the platforms using a receiver operating characteristic (ROC) curve analysis to measure area under the curve (AUC)...
January 11, 2017: ALTEX
https://www.readbyqxmd.com/read/28069986/mechanisms-involved-in-porcine-early-embryo-survival-following-ethanol-exposure
#4
Florence Pagé-Larivière, Céline Campagna, Marc-André Sirard
Alcohol consumption during pregnancy is still a cause of preventable birth defects and developmental disabilities. However, little is known about the impact of ethanol on preimplantation embryos and the molecular mechanisms involved. We aimed to determine the toxicogenomic impacts and the mechanisms involved in preimplantation embryonic survival following 0.2% ethanol exposure in porcine embryos. Gene expression changes were measured with a porcine embryo specific microarray and confirmed by RT-qPCR. Compared to control, ethanol exposure led to a 43% decrease in blastocyst rate and activated pathways associated with oxidative stress and nervous system damage, such as TP53 and TGF...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28063342/linking-genomic-responses-of-gonads-with-reproductive-impairment-in-marine-medaka-oryzias-melastigma-exposed-chronically-to-the-chemopreventive-and-antifouling-agent-3-3-diindolylmethane-dim
#5
Lianguo Chen, Doris W T Au, Chenyan Hu, Weipeng Zhang, Bingsheng Zhou, Lin Cai, John P Giesy, Pei-Yuan Qian
3,3'-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28days) aqueous exposure to relatively low doses (0μg/L or 8.5μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway...
December 30, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28033256/identified-molecular-mechanism-of-interaction-between-environmental-risk-factors-and-differential-expression-genes-in-cartilage-of-kashin-beck-disease
#6
Fang-Fang Yu, Yan-Xiang Zhang, Lian-He Zhang, Wen-Rong Li, Xiong Guo, Mikko J Lammi
As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28032149/dtni-a-novel-toxicogenomics-data-analysis-tool-for-identifying-the-molecular-mechanisms-underlying-the-adverse-effects-of-toxic-compounds
#7
Diana M Hendrickx, Terezinha Souza, Danyel G J Jennen, Jos C S Kleinjans
Unravelling gene regulatory networks (GRNs) influenced by chemicals is a major challenge in systems toxicology. Because toxicant-induced GRNs evolve over time and dose, the analysis of global gene expression data measured at multiple time points and doses will provide insight in the adverse effects of compounds. Therefore, there is a need for mathematical methods for GRN identification from time-over-dose-dependent data. One of the current approaches for GRN inference is Time Series Network Identification (TSNI)...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28008973/disentangling-genetic-and-environmental-risk-factors-for-individual-diseases-from-multiplex-comorbidity-networks
#8
Peter Klimek, Silke Aichberger, Stefan Thurner
Most disorders are caused by a combination of multiple genetic and/or environmental factors. If two diseases are caused by the same molecular mechanism, they tend to co-occur in patients. Here we provide a quantitative method to disentangle how much genetic or environmental risk factors contribute to the pathogenesis of 358 individual diseases, respectively. We pool data on genetic, pathway-based, and toxicogenomic disease-causing mechanisms with disease co-occurrence data obtained from almost two million patients...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27984170/autism-genes-are-selectively-targeted-by-environmental-pollutants-including-pesticides-heavy-metals-bisphenol-a-phthalates-and-many-others-in-food-cosmetics-or-household-products
#9
REVIEW
C J Carter, R A Blizard
The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin)...
October 27, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#10
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27957850/comparative-toxicogenomic-responses-to-the-flame-retardant-mitp-in-developing-zebrafish
#11
Derik E Haggard, Siba R Das, Robert L Tanguay
Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping failure. Mechanistic studies showed that mITP is an aryl hydrocarbon receptor (AhR) ligand; however, the cardiotoxic effects of mITP were independent of the AhR. We performed comparative whole genome transcriptomics in wild-type and ahr2(hu3335) zebrafish, which lack functional ahr2, to identify transcriptional signatures causally involved in the mechanism of mITP-induced cardiotoxicity...
December 13, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27928627/recommended-approaches-in-the-application-of-toxicogenomics-to-derive-points-of-departure-for-chemical-risk-assessment
#12
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
#13
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
#14
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
#15
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
#16
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)...
February 2017: 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
#17
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
#18
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
#19
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
#20
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
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