Genome-wide transcriptional responses to benzo[a]pyrene and clofibrate in the tunicate Oikopleura dioica
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ABSTRACT:
ORGANISM(S): Oikopleura dioica
PROVIDER: GSE33818 | GEO | 2013/02/05
SECONDARY ACCESSION(S): PRJNA148149
REPOSITORIES: GEO
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Project description:Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics are not known in most invertebrates. Here, using high density tiling arrays with over 2 million probes, we explored genome-wide gene expression in the tunicate Oikopleura dioica in response to two model xenobiotic chemicals – the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo). The genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes, as in vertebrates. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. Oikopleura appears to have basic defensome toolkit consisting of phase I, phase II and phase III biotransformation genes. Exposure of about 130 four-days-old animals in 1L seawater in glass beakers. Pooled animals used, no replicates. DMSO Treatments: -Clofibrate (Clo) (Sigma-Aldrich, St. Louis, MO): 1 µM and 5 µM. -Benzo[a]pyrene (BaP (Sigma-Aldrich): 0.2 µM and 1 µM - Controls received 1 ml Dimethyl sulfoxide (DMSO). -The animals kept at room temperature and harvested after 10 hrs and frozen. -Total RNA was isolated from the pooled animals using the RNeasy Mini Kit according to manufacturer’s protocols (QIAGEN, Hilden, Germany). - 5 µg total RNA was converted to dscDNA using SuperScript Double-Stranded cDNA Synthesis Kit (Invitrogen, Carlsbad, CA), and dscDNA samples were submitted for microarray analysis. BaP and Clo treated samples were labeled using Cy3-coupled random nonamers and DMSO controls were labeled using Cy5-coupled random nonamers. Total 4 hybridizations for the 8 samples (single hybridization for each treatment and DMSO control pair), no replicates.
2013-02-05 | E-GEOD-33818 | biostudies-arrayexpress
Project description:Gene expression changes to the chemical compound BaP in livers of wildtype and Xpa-/-p53+/- mice
2014-06-01 | E-MTAB-1247 | biostudies-arrayexpress
Project description:Polycyclic aromatic hydrocarbons (PAHs) are abundant organic compounds and are anthropogenically produced by the incomplete combustion of organic matter (e.g. fossil fuels and tobacco smoke). One notable model PAH is benzo[a]pyrene (BaP), which is listed as a Group 1 human carcinogen by the International Agency of Research on Cancer (IARC). Although the mode of action for BaP is well known in higher organisms, limited knowledge is available regarding the consequence of BaP exposure in the model organism Caenorhabditis elegans. The objective of this study was to define the the global transcriptome of wild-type C. elegans exposed to BaP (0, 5 and 20 μM). The most responsive transcripts were linked to redox processes and xenobiotic responses, including P450 enzymes (CYPs) (mainly members of the CYP35 family), epoxide hydrolases (EHs), glutathione S-transferases (GSTs), and UDP-glucuronosyltransferases (UGTs), all of which are linked to the metabolism (phase I & II) of xenobiotic substances. In summary, although the dominant CYP1A1/2 & CYP1B1 metabolic pathway is absent in C. elegans, BaP still induced a strong transcriptomic response. This provides strong evidence that parallel pathway(s) are implicated in BaP metabolism, and possibly, in its detoxification.
2021-03-03 | GSE152257 | GEO
Project description:Benzo[a]pyrene (BaP) is a very extensively studied prototypical polycyclic aromatic hydrocarbons (PAHs). Previous work in our laboratory showed no changes of microRNA (miRNA) expression in liver following a 3 days exposure to BaP, suggesting a lack of miRNA transcriptional responses to aryl hydrocarbon receptor agonists and/or DNA damage. Here, we studied 25-week old male MutaTM Mouse exposed to 25, 50, and 75 mg/kg/day BaP by oral gavage for 28 consecutive days. MAANOVA identified 110 differentially expressed genes (adjusted p < 0.05) with fold change greater than 1.5. The genes most affected included those involved in xenobiotic metabolism, phase II metabolizing enzymes, as well as the downstream targets of p53. Pathway specific RT-PCR was used to confirm the p53 response. A single significant increase in miRNA expression was identified (mir-34a and validated using the Qiagen miScript PCR system). This miRNA is known to be transcriptionally activated by p53. Ingestion of BaP leads to widespread changes in gene expression in mouse liver, with enrichment of genes involved in cell cycle arrest, DNA damage response, and apoptosis via the p53 pathway. In contrast, miRNA expression was relatively unaffected. Only miR-34a was significantly up-regulated, and may therefore play a critical role in the post-transcriptional regulation of p53 and/or its downstream targets. Keywords: Agilent mouse 4 x 44 oligonucleotide microarrays were used to assess global gene expression in response to 25, 50, and 75 mg/kg BaP treatment
2011-10-19 | GSE24907 | GEO
Project description:Benzo[a]pyrene (BaP) is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage with along the activation of the aryl hydrocarbon receptor (AHR) induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP for 12 h. Agilent Whole Human 44K Genome Oligo Arrays and RT-PCR were used to detect gene expression (mRNA) changes. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-concentrated cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins, which implies that proliferating cells are more prone to DNA damage by genotoxic stress than non-proliferating cells, due to variation in the efficiency of BaP metabolism through the cell cycle. This study suggests that growth kinetics within a target-cell population may be an important parameter in determining susceptibility to exposure to a genotoxic agent. KEYWORDS: Carcinogen treatment Two-color Agilent array. A reference design was chosen that all samples were hybridised to universal human reference RNA (UHRR from stratagene). 8-condition experiment (4 conditions: G0/G1, S, G2/M and unsynchronised (N); 2 treatments: BaP and DMSO; 1 time point: 12 hours). Three biological replicates for each condition. One replicate per array.
2012-02-02 | E-GEOD-26917 | biostudies-arrayexpress
Project description:Benzo[a]pyrene (BaP) is a very extensively studied prototypical polycyclic aromatic hydrocarbons (PAHs). Previous work in our laboratory showed no changes of microRNA (miRNA) expression in liver following a 3 days exposure to BaP, suggesting a lack of miRNA transcriptional responses to aryl hydrocarbon receptor agonists and/or DNA damage. Here, we studied 25-week old male MutaTM Mouse exposed to 25, 50, and 75 mg/kg/day BaP by oral gavage for 28 consecutive days. MAANOVA identified 110 differentially expressed genes (adjusted p < 0.05) with fold change greater than 1.5. The genes most affected included those involved in xenobiotic metabolism, phase II metabolizing enzymes, as well as the downstream targets of p53. Pathway specific RT-PCR was used to confirm the p53 response. A single significant increase in miRNA expression was identified (mir-34a and validated using the Qiagen miScript PCR system). This miRNA is known to be transcriptionally activated by p53. Ingestion of BaP leads to widespread changes in gene expression in mouse liver, with enrichment of genes involved in cell cycle arrest, DNA damage response, and apoptosis via the p53 pathway. In contrast, miRNA expression was relatively unaffected. Only miR-34a was significantly up-regulated, and may therefore play a critical role in the post-transcriptional regulation of p53 and/or its downstream targets. Keywords: Agilent mouse 4 x 44 oligonucleotide microarrays were used to assess global gene expression in response to 25, 50, and 75 mg/kg BaP treatment Individual total RNA (200 ng) from 5 mice per treatment group (control, 24mg/kg, 50mg/kg, and 75mg/kg) and universal reference total RNA (Stratagene, Mississauga, ON, Canada) was used to synthesize double stranded cDNA.
2011-10-18 | E-GEOD-24907 | biostudies-arrayexpress
Project description:BACKGROUND: Benzo[a]pyrene (BaP) is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR) induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA) changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP) 1A1 and CYP1B1, which are involved in BaP metabolism. RESULTS: Following BaP exposure, cells evaded G1 arrest and accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M- compared with G0/G1-enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE), the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle. CONCLUSIONS: This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell cycle. Our results suggest that growth kinetics within a target-cell population may be important determinants of susceptibility and response to a genotoxic agent.
2012-02-02 | GSE26917 | GEO
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9â°. The two other groups were injected with NaCl 9â° alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608.
2008-06-19 | E-GEOD-2216 | biostudies-arrayexpress
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9‰. The two other groups were injected with NaCl 9‰ alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608. Keywords = Clofibric acid Keywords = Diethylnitrosamine Keywords = Rat Keywords: other
2005-03-01 | GSE2216 | GEO
Project description:Benzo[a]pyrene (BaP) is a very extensively studied prototypical polycyclic aromatic hydrocarbons (PAHs). Previous work in our laboratory showed no changes of microRNA (miRNA) expression in liver following a 3 days exposure to BaP, suggesting a lack of miRNA transcriptional responses to aryl hydrocarbon receptor agonists and/or DNA damage. Here, we studied 25-week old male MutaTM Mouse exposed to 25, 50, and 75 mg/kg/day BaP by oral gavage for 28 consecutive days. MAANOVA identified 110 differentially expressed genes (adjusted p < 0.05) with fold change greater than 1.5. The genes most affected included those involved in xenobiotic metabolism, phase II metabolizing enzymes, as well as the downstream targets of p53. Pathway specific RT-PCR was used to confirm the p53 response. A single significant increase in miRNA expression was identified (mir-34a and validated using the Qiagen miScript PCR system). This miRNA is known to be transcriptionally activated by p53. Ingestion of BaP leads to widespread changes in gene expression in mouse liver, with enrichment of genes involved in cell cycle arrest, DNA damage response, and apoptosis via the p53 pathway. In contrast, miRNA expression was relatively unaffected. Only miR-34a was significantly up-regulated, and may therefore play a critical role in the post-transcriptional regulation of p53 and/or its downstream targets. Keywords: Agilent mouse 8 x 15K miRNA microarray system with miRNA complete labeling and hyb kit were used to assess miRNA expression in response to 25, 50, and 75 mg/kg BaP treatment RNA samples from 3 control and 5 mice per treatment group (24mg/kg, 50mg/kg, and 75mg/kg) containing 100 ng were labelled using Agilent?s miRNA complete labelling and Hyb Kit (Agilent Tech, Mississauga, ON, Canada).
2011-10-18 | E-GEOD-24909 | biostudies-arrayexpress