Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA206184 | ENA |
REPOSITORIES: ENA
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Project description:Acrylamide is a reproductive toxicant that has been detected in foods such as potato chips and breads. The consequences of chronic exposure to acrylamide in the human diet are unknown; however we previously reported that exposure to acrylamide at levels equivalent to human exposure produced high levels of genetic damage in early male germ cells of mice [Nixon et al. ToxSci 129(1), 135–145 (2012)]. In the present study, we examined changes in testicular gene expression in these mice to examine the potential mechanisms involved in acrylamide induced DNA damage in male germ cells and to provide a better understanding of the reproductive toxic effects of acrylamide in the male. Adult male mice were subjected to chronic acrylamide exposure via the drinking water at concentrations of 0, 0.001, 0.01, 0.1, 1 and 10 µg/ml for 1, 6 and 12 months. The testes were collected at each time point for RNA extraction and hybridization on an Illumina Sentrix Mouse ref-8 v2 Beadchip.
2014-06-01 | E-GEOD-47574 | biostudies-arrayexpress
Project description:Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis, such as DNA repair, DNA replication, chromosome segregation, among others, animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, T3 and T4, were increased in acrylamide-treated rats sampled at night, but not in quiescent animals, compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.
2014-10-06 | GSE62026 | GEO
Project description:Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure.
2012-02-08 | GSE29004 | GEO
Project description:Acrylamide, a high-production-volume chemical and food contaminant in baked and fried carbohydrate-rich foods has been classified as a “Group 2A carcinogen” (probable human carcinogen) by the IARC. The carcinogenicity of acrylamide is attributed to its well-recognized genotoxicity; however, evidence suggests that acrylamide may also induce non-genotoxic alterations. In the present study female B6C3F1 mice were exposed to 0.70mM acrylamide in drinking water for 28 days and genotoxic and transcriptomic effects were investigated in the lung, a target organ for acrylamide carcinogenicity in mice, and the liver, a non-target organ. Acrylamide exposure resulted in a dose-dependent formation of N7-(2-carbamoyl-2-hydroxyethyl)guanine and N3-(2-carbamoyl-2-hydroxyethyl)adenine in lung and liver DNA at the similar levels. In contrast, whole genome gene expression profiles in the lungs and livers revealed the tissue-specific gene expression alterations. By using a SurePrint G3 Mouse Gene Expression v2 8x60K Microarray Kit (Agilent Technologies), we identified 123 and 363 genes that were found to be differentially expressed in the lungs and livers of acrylamide-treated mice; however, only 5 genes were in common between the organs. A detailed analysis of differentially expressed genes revealed that the major difference in the effect of acrylamide on the transcriptome in the lungs and livers was related to a different trend of gene expression changes. In the lungs, acrylamide exposure caused an inhibition of gene expression (54 up-regulated and 69 down-regulated genes), whereas the opposite effect, characterized by twice the number of up-regulated as compare to down-regulated genes (245 up-regulated and 118 down-regulated), was found in the livers of exposed mice.
2019-01-30 | GSE125851 | GEO
Project description:Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. The persistence and widespread distribution of these compounds in humans have brought them under intense scrutiny. Limited pharmacokinetic data is available in humans; however, human data exists for two communities with drinking water contaminated by PFAAs. Also, there is toxicological and pharmacokinetic data for monkeys, which can be quite useful for cross-species extrapolation to humans. The goal of this research was to develop a physiologically-based pharmacokinetic (PBPK) model for PFOA and PFOS for monkeys and then scale this model to humans in order to describe available human drinking water data. The monkey model simulations were consistent with available PK data for monkeys. The monkey model was then extrapolated to the human and then used to successfully simulate the data collected from residents of two communities exposed to PFOA in drinking water. Human PFOS data is minimal; however, using the half-life estimated from occupational exposure, our model exhibits reasonable agreement with the available human serum PFOS data. It is envisioned that our PBPK model will be useful in supporting human health risk assessments for PFOA and PFOS by aiding in understanding of human pharmacokinetics.
Model is encoded by Ruby and submitted to BioModels by Ahmad Zyoud
2020-03-20 | MODEL2003190002 | BioModels
Project description:Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure. Three-week-old male Wistar rat pups were treated with either acrylamide or saline daily (30 mg/kg) for 21 days, then tissues (cerebellum, spinal cord, and sciatic nerve) were harvested and frozen. Two biological replicate samples, each sample consisting of pooled tissue from 2 rats, were analyzed for each treatment.
2012-02-08 | E-GEOD-29004 | biostudies-arrayexpress
Project description:Here we investigated the longterm carryover effects of dichloroacetic acid (DCA), a common by-product of drinking water chlorination, on hepatic tumorigenesis in mice. Our findings demonstrate that postnatal exposure to a common drinking water contaminant results in longterm carryover effects on tumorigenesis, potentially via epigenetic events altering cellular respiration and metabolism.
2015-02-26 | GSE58585 | GEO
Project description:Background: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. We isolate total RNA from 72 mouse whole blood samples. These included samples following a 2-week exposure to lead acetate trihydrate (untreated controls = 7; Low Pb 5ug/mL drinking water = 15; High Pb 50ug/mL drinking water = 15) and additional samples following a 2-week recovery period with plain drinking water (untreated controls = 7; Low Pb group = 15; High Pb group = 13).
2011-03-30 | E-GEOD-28261 | biostudies-arrayexpress
Project description:Purpose: In testis the effects of exposure to mixtures of Endocrine disruptors compounds (EDCs) upon expression of miRNAs were not addressed. Objective: To identify the expression profiles of the 'miRNome' in mice testis chronic exposed to a defined mixture of five EDCs. Methods: Pregnant mice from 0.5 post-coital day were exposed in the drinking water to a mixture containing 0.3 mg/Kg-bw/day of each phthalate (DEHP, DBP, BBP), plus 0.05 mg/Kg-bw/day of each alkylphenol (NP, OP) until adulthood of male mouse (60 days old). We characterized the 'miRNome' by next generation sequence (NGS). Results: In mouse testis exposed to EDCs mixture we detected by NGS 2 up-regulated and 8 down-regulated miRNAs along to 36 isomiRs differentially expressed; these results were validated by RT-qPCR. and functional analysis showed deregulation of testicular hormonal status, spermatogenesis disruption and germ cells apoptosis. Conclusions: Here we provide the first association between deregulation of miRNAs, isomiRs, with histopathological and hormonal alterations in adult mice testis exposed to mixture of EDCs.
2017-07-31 | GSE84695 | GEO
Project description:Here we investigated the longterm carryover effects of dichloroacetic acid (DCA), a common by-product of drinking water chlorination, on hepatic tumorigenesis in mice. Our findings demonstrate that postnatal exposure to a common drinking water contaminant results in longterm carryover effects on tumorigenesis, potentially via epigenetic events altering cellular respiration and metabolism. The gene expression study followed a stop-promotion design in which 7d male B6C3F1 mice received the following treatments: deionized water alone (dH2O, control); 0.06% phenobarbital (PB), a rodent liver mitogen and tumor promoter; or DCA (3.5g/L) for 10 weeks followed by dH2O for 90 weeks.
2015-02-26 | E-GEOD-58585 | biostudies-arrayexpress