3-Methylcholanthrene treated Rat
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE3175 | GEO | 2005/12/22
SECONDARY ACCESSION(S): PRJNA92719
REPOSITORIES: GEO
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Project description:Analysis of transcriptional response changes in rats after treatment with 3-Methylcholanthrene Rats were treated with 3-methylcholanthrene (MC) (100 umol/kg) in corn oil (CO) (2 ml/kg), or were given equal volumes of CO, i.p., once daily for 4 days. At 1, 15, and 28 day time points, the animals were sacrificed, and livers were stored at -800 C for later isolation of RNA. Gene expression was studied by cDNA microarray analyses. The analyses was conducted in the laboratory of Dr. Chris Bradfield of the University of Wisconsin. Gene expression was monitored using 4572 unique clones from liver-derived EST libraries fortified with clones of known liver genes representing ~4000 genes. These cDNAs represented toxicologically relevant genes such as drug metabolizing enzymes (e.g. P450s), inflammatory responsive genes (e.g. SAA-1), and genes that were previously identified as useful in classification of chemicals. All clones were then sequence verified from both 3’ and 5’ directions. Six replicates of each cDNA were printed on each array using a Microgrid II (Biorobotics, Woburn, MA). The labeled cDNA from both the MC-treated groups and from a pool of the corresponding controls were mixed and hybridized to the liver microarray for 18 h according to the Genisphere (Hatfield, PA) protocol, as described in EDGE, a scientific resource for toxicology-related gene expression information (University of Wisconsin, Madison)
2005-12-22 | E-GEOD-3175 | biostudies-arrayexpress
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2007-12-23 | GSE10015 | GEO
Project description:TCE is a non-genotoxic hepatocarcinogen in mouse, but not in rat or human. Extrapolation of data from laboratory animals to humans is difficult due to species-specific differences. To identify molecular pathways and biological changes responsible for species-specific differences in hepatocarcinogenesis, we analyzed gene expression profiles of livers from B6C3F1 mice and SD rats administered TCE by oral gavage once or repeatedly every 24 hrs for 14 days. Gene expression analysis revealed distinct clusters of transcriptional profiles in single- and repeated-dose mice and rats. Pathway analysis showed differences in biological pathways between single- and repeated-dose mice and rats. Activation of the MAPK signaling cascade and ubiquitin-proteasome inhibitory function, as well as inhibition of TGF-beta signaling, were specific to mice and suggest a role in hepatocyte proliferation. Although pathological analysis showed no evidence of apoptosis, gene expression analysis revealed changes in apoptosis-related genes. In addition to the previously reported suppression of apoptosis, results in repeated-dose mice showed that toxicity induced by TCE in turn induces apoptosis. Keywords: Response to chemical
2008-12-25 | GSE10823 | GEO
Project description:Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Exiqon miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused few changes in miRNA levels in rat livers and those changes that were statistically significant were of modest magnitude. AHR genotype had little effect on hepatic miRNA levels, either in constitutive expression or in response to TCDD – only a few miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver. We conducted a thorough investigation to address the following questions: (1) does AHR genotype itself affect constitutive expression of microRNAs? (2) does TCDD affect microRNA levels and, if so, is this response dependent on the AHR? (3) does TCDD affect microRNA levels differently in animals that are sensitive to dioxin toxicity versus those that are dioxin-resistant? We assessed the in vivo effect of TCDD on microRNA levels in liver at multiple time points after TCDD treatment using microRNA arrays along with quantitative RT-PCR. The cumulative results of our experiments indicate that downregulation of mRNA levels by dioxins in adult rodent livers is very unlikely to involve microRNAs. Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007. Keywords: miRNA expression, Time course, response to xenobiotics, genetic modification, comparative genome hybridization We examined strain differences in miRNA expression independent of TCDD: 19-h vehicle-treated dioxin-resistant H/W AHRH/W/H/W rats (HC19) vs. vehicle- control dioxin-sensitive L-E AHRWT/WT rats (LC19). In the dioxin-sensitive rats we compared miRNA expression levels 3 h (LT3) or 19 h (LT19) post-TCDD treatment vs. LC19. In the dioxin-resistant rats we compared miRNA levels 3 h (HT3), 19 h (HT19), or 96 h (HT96) post-TCDD treatment vs. HC19.
2007-08-15 | E-GEOD-8470 | biostudies-arrayexpress
Project description:Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Ambion miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused no significant changes in miRNA levels in rat livers. AHR genotype had no effect on hepatic miRNA levels in response to TCDD – no miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver. Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007. Keywords: miRNA expression, response to xenobiotics, genetic modification, comparative genome hybridization In the dioxin-sensitive L-E rats we compared miRNA expression levels 19 h post-TCDD treatment vs. corn oil vehicle treatment. In the dioxin-resistant H/W rats we compared miRNA levels 19 h post-TCDD treatment vs.corn oil vehicle treatment.
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Project description:Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Ambion miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused no significant changes in miRNA levels in rat livers. AHR genotype had no effect on hepatic miRNA levels in response to TCDD – no miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver. Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007. Keywords: miRNA expression, response to xenobiotics, genetic modification, comparative genome hybridization
2007-08-15 | GSE8467 | GEO
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