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ABSTRACT:
PROVIDER: PRJNA263137 | ENA |
REPOSITORIES: ENA
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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 (AA) is known to produce tumors in animals in different tissues including the thyroid where typically the tumors are found in follicular cells in the thyroid gland. Using transcriptomic tools, we examined global gene expression changes in the thyroid glands of RccHan Wistar rats that were sub-chronically exposed to a low dose of AA (3 mg/Kg). A transcriptomic approach was used to investigate changes in gene expression and their association with physiological responses (changes in plasma hormone levels) in rats treated with acrylamide (AA), exposed from gestational day 6 to post natal day 21. We hypothesized that 3 mg AA/Kg bw/day exposure would produce changes in plasma hormone levels associated with key genes and biochemical pathways involved with molecular actions of AA.
2014-10-06 | E-GEOD-62026 | biostudies-arrayexpress
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: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, 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:Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate. Nine female rats were fed drinking water containing 0.1ppb Roundup formulation (50 ng/L glyphosate equivalent dilution). Ten control female rats were fed untreated drinking water. Samples of liver and kidney were taken for gene expression analysis.
2015-09-04 | E-GEOD-66059 | biostudies-arrayexpress
Project description:Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate. Ten female rats were fed drinking water containing 0.1ppb Roundup formulation (50 ng/L glyphosate equivalent dilution). Ten control female rats were fed untreated drinking water. Samples of liver and kidney were taken for gene expression analysis.
2015-09-04 | E-GEOD-66058 | biostudies-arrayexpress
Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Experiment Overall Design: Male C57BL/6 mice, fed on two commercially available laboratory diets (LRD-5001 and AIN-76A), were chronically exposed through drinking water or food, to environmentally relevant concentrations of sodium arsenite. Another group animals, fed on the AIN 76A diet, was IP injected with dexamethasone (1 mg/kg), sodium arsenite (1mg/kg), both dexamethosone and arsenite, or saline alone.
2008-10-21 | E-GEOD-11056 | biostudies-arrayexpress
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:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with; chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows,; but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Experiment Overall Design: Male C57BL/6 mice, fed on two commercially available laboratory diets (LRD-5001 and AIN-76A), were chronically exposed through drinking water or food, to environmentally relevant concentrations of sodium arsenite. Experiment Overall Design: Another group animals, fed on the AIN 76A diet, was IP injected with dexamethasone (1 mg/kg), sodium arsenite (1mg/kg), both dexamethosone and arsenite, or saline alone.
2008-06-16 | E-GEOD-9630 | biostudies-arrayexpress