DNA methylation changes by furan in Sprague Dawley rat liver
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Tao chen
PROVIDER: E-MTAB-716 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Furan is a widely used industrial chemical and a common contaminant in heated foods. Chronic furan exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors at doses of 2 mg/kg bw/day with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those inducing liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced hepatotoxicity in males included gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses (regeneration). Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional BMDs could be examined in males, they ranged from 0.08 – 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a target of P53 signalling) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence in support of the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences. Total RNAs from 16 liver samples (4 males and 4 females from control and 2 mg/kg bw/day dose groups) were processed using the miRNA Complete Labelling and Hybridization kit (Agilent Technologies Inc.). Labelled RNA was hybridized on 8 X 15K Agilent rat miRNA microarray slides. Arrays were scanned using an Agilent G2505B scanner (5 ?M resolution). Feature extraction (version 10.7.3.1, Agilent Tech. Inc.) was used to acquire the fluorescence intensity of each probe.
2014-10-30 | E-GEOD-62807 | biostudies-arrayexpress
Project description:Furan is a widely used industrial chemical and a common contaminant in heated foods. Chronic furan exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors at doses of 2 mg/kg bw/day with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those inducing liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced hepatotoxicity in males included gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses (regeneration). Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional BMDs could be examined in males, they ranged from 0.08 M-bM-^@M-^S 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a target of P53 signalling) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence in support of the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences. A total of 50 RNA samples (5 female and 5 male rats per dose group, 5 dose groups total) were labelled with Cyanine 5-CTP using Low Input Quick Amp Labelling kits (Agilent Technologies Inc.) following the manufacturerM-bM-^@M-^Ys instruction. Universal rat reference total RNA (Agilent Technologies Inc.) was labelled with Cyanine 3-CTP. Cy5-sample cRNA and Cy3-reference cRNA were hybridized to Agilent G4853A SurePrint G3 Rat GE 8 X 60K microarrays (Agilent Technologies Inc.). One microarray from the male group did not pass the quality control and was eliminated from further analyses
2014-10-30 | E-GEOD-62806 | biostudies-arrayexpress
Project description:Male Sprague Dawley Crl CD BR rats (190-240g, 6-8 weeks old), were obtained from Charles River, UK. They were given access to R&M No.1 diet and tap water ad libitum. Animals were housed 5/sex in solid bottom cages maintained at 21oC +/- 2oC, 12 h light and 12 h dark. All animals were acclimatised for at least 5 days prior to commencement of the study. Furan (CAS 110-00-9, Sigma-Aldrich Co. Ltd, >99 % pure was prepared in corn oil vehicle on the day of use and stored in sealed brown bottles. Furan was administered orally via gavage in corn oil at 30mg/kg (5 daily doses per week). Animals (n=5) were removed and sampled after 3 months of furan treatment. An off-dose recovery group was included at the 3 month time point (1 month off-dose) to enable assessment of lesion reversibility.
2008-04-01 | E-MEXP-1421 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. Adult female B6C3F1 mice were exposed to 1, 2, 4 or 8 mg/kg bw furan or vehicle control (corn oil) for three weeks and sacrificed four hours after the final exposure. In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice exposed to furan for 3 weeks at four different doses: 1, 2, 4 or 8 mg/kg bw furan (or vehicle control) and sacrificed four hours after the final exposure. Each dose group had 4-5 biological replicates. There were a total of 25 samples included in the final analysis. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent).
2014-01-10 | E-GEOD-48644 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-30 | E-GEOD-62808 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice to BrdU treatment (in drinking water for 5 days before sacrifice). This was a toxicogenomic study in which mice were also exposed to 0, 1 or 8 mg/kg bw furan (by oral gavage) for 3 weeks. Mice were sacrificed four hours after the final furan exposure. Each dose group had 4-5 biological replicates. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent). Please note that data for all non-BrdU treated animals was previously reported in GEO [GSE48644]. All samples (with or without BrdU) were part of the same randomized block design for the microarrays.
2014-07-01 | E-GEOD-54078 | biostudies-arrayexpress
Project description:We describe furan as a triggerable ‘warhead’ for site-specific cross-linking using the actin and thymosin β4 (Tβ4)-complex as model of a weak and dynamic protein-protein interaction with known 3D structure and with application potential in disease contexts. The presented in vitro validation of covalently acting ‘furan-armed’ Tβ4-variants provides initial proof to further exploit furan-technology for covalent drug design.
2021-05-13 | PXD025066 | Pride
Project description:Furan is a heterocyclic organic compound produced in the chemical manufacturing industry and also found in a broad range of food products, including infant formulas and baby foods. Previous reports have indicated that the adverse biological effects of furan, including its liver tumorigenicity, may be associated with epigenetic abnormalities. In the present study we investigated the persistence of epigenetic alterations in rat liver. Male Fisher 344 (F344) rats were treated by gavage 5 days per week with 8 mg furan/kg body weight (bw)/day for 90 days. After the last treatment, rats were divided randomly into four groups; one group of rats was sacrificed 24 hours after the last treatment, while other groups were maintained without further furan treatment for an additional 90, 180, or 360 days. Treatment with furan for 90 days resulted in alterations in histone lysine methylation and acetylation, oxidative damage to DNA, and changes in the gene expression in the livers. A majority of these furan-induced molecular changes was transient and disappeared after the cessation of furan treatment. In contrast, histone H3 lysine 9, H3 lysine 27, and H3 lysine 56 showed a sustained and time-depended decrease in acetylation, which was associated with formation of heterochromatin and altered gene expression. These results indicate that furan-induced adverse effects may be mechanistically related to sustained changes in histone lysine acetylation that compromise the ability of cells to maintain and control properly the expression of genetic information.
2014-12-02 | GSE63740 | GEO
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action.
2014-07-01 | GSE54078 | GEO
Project description:In this study, we evaluated the utility of microRNA (miRNA) profiling in female B6C3F1 mouse liver to indicate mechanisms of liver perturbation due to short-term exposure of the known rodent liver hepatotoxicant and carcinogen, furan. Analyses indicated a robust dose response for 34 miRNAs to furan and involvement of p53-linked pathways in furan-mediated hepatotoxicity. Overall, these results indicate mechanistic involvement of miRNA in furan carcinogenicity and provide evidence of their potential utility as accessible biomarkers of exposure and disease.
2023-09-05 | GSE224206 | GEO