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Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (miRNA)

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE24909 | GEO | 2011/10/19

SECONDARY ACCESSION(S): PRJNA133401

REPOSITORIES: GEO

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Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (miRNA)

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

Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (gene expression)

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

Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (gene expression)

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

Pulmonary gene expression in MutaTMMouse orally gavaged with three doses of benzo(a)pyrene and vehicle control

2012-10-03 | GSE35718 | GEO

Pulmonary gene expression in MutaTMMouse orally gavaged with three doses of benzo(a)pyrene and vehicle control

Project description:In this study, we investigate mRNA profiles in lung of mice exposed to benzo(a)pyrene. Male mice were exposed to three doses (25, 50, and 75 mg/kg/day BaP) for 28 days and profiles were examined three days post-exposure. Our analyses reveal that BaP causes pulmonary specific cellular transformation indicative of carcinogenesis. Individual total RNA (200 ng) from 5 mice per treatment group (control, 25mg/kg/day, 50mg/kg/day, and 75mg/kg/day) and universal reference total RNA (Stratagene, Mississauga, ON, Canada) was used to synthesize double stranded cDNA.

2012-10-03 | E-GEOD-35718 | biostudies-arrayexpress

Lack of hepatic response of microRNA in mice following DB[a,h]A exposure (Agilent miRNA)

Project description:Dibenzo[a,h]anthracene DB[a,h]A is a polycyclic aromatic hydrocarbon potent carcinogen. Few studies have investigated the role of DB[a,h]A on mRNA and miRNA expression. In this study a 10-week old male MutaTM Mouse were exposed to 6.25, 12.5, and 25 mg/kg/day DB[a,h]A by oral gavage for 28 consecutive days. DNA adducts were detected in the livers at each DB[a,h]A dose tested, and a dose-dependent increase in lacZ mutants was observed in the same samples. MAANOVA analysis revealed minor changes in the mRNA expression for the two lowest doses. Differential expression of 19 up-regulated and 22 down-regulated transcripts with fold-change > 1.5 (FDR-adjusted P < 0.05) were identified in the 6.25 mg/kg/day DB[a,h]A treatment group. For the 12.5 mg/kg/day treatment group 13 transcripts were up-regulated and 32 down-regulated (FDR-adjusted P < 0.05 and fold-change > 1.5). Major effect on mRNA expression resulted from exposure to the highest dose (25 mg/kg/day) of DB[a,h]A with 135 up-regulated and 104 down-regulated genes with fold-change > 1.5 (FDR-adjusted P < 0.05). The significantly regulated genes are involved in circadian rhythm, drug metabolism, glucose metabolism, cholestrol and lipid metabolism, immune response, cell cycle, and apoptosis. We also investigated miRNA response to the three doses of DB[a,h]A. MiRNA expression was relatively unaffected. Only miR-34a showed significant (FDR-adjusted P < 0.05) up-regulation with a fold change above 1.3-fold. RNA samples from 5 control and 4-5 mice per treatment group (6.25mg/kg, 12.50mg/kg, and 25mg/kg) containing 100 ng were labelled using AgilentM-bM-^@M-^Ys miRNA complete labelling and Hyb Kit (Agilent Tech, Mississauga, ON, Canada).

2013-07-02 | E-GEOD-35195 | biostudies-arrayexpress

MicroRNA expression profiling in adult mouse liver following benzo(a)pyrene (BaP) treatment [Agilent miRNA array]

Project description:Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene (BaP), as detected using Agilent miRNA arrays. We have investigated the effect of exposure to 150 mg/kg benzo(a)pyrene (BaP) for 3 days on mRNA and miRNA expression levels in adult mouse liver. We used Agilent miRNA array platforms to assess effects of BaP exposure on miRNA expression levels. Our results indicate a distinct lack of effect of BaP of miRNA expression, despite widespread changes in mRNA levels. Keywords: Toxicology, miRNA

2010-10-18 | GSE18786 | GEO

MicroRNA expression profiling in adult mouse liver following benzo(a)pyrene (BaP) treatment [Exiqon miRNA array]

2010-10-18 | GSE18782 | GEO

Reference: MicroRNA expression profiling in adult mouse liver following BaP treatment [Agilent miRNA array]

Project description:We have investigated the effect of exposure to 150 mg/kg benzo(a)pyrene (BaP) for 3 days on mRNA and miRNA expression levels in adult mouse liver. We used Agilent miRNA array platforms to assess effects of BaP exposure on miRNA expression levels. Our results indicate a distinct lack of effect of BaP of miRNA expression, despite widespread changes in mRNA levels. The data in the attached array files were used a positive control for the Agilent platform, to indicate that the platform was able to detect significant differences in abundance of miRNA between two samples with great differences in miRNA content. Keywords: Toxicology, miRNA

2010-10-28 | GSE19438 | GEO

MicroRNA expression profiling in adult mouse liver following benzo(a)pyrene (BaP) treatment [Exiqon miRNA array]

Project description:Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene (BaP), as detected using Exiqon miRNA arrays. Adult male mice were exposed to 150 mg/kg benzo(a)pyrene (BaP) or solvent for 3 days and sampled 4 hours after the last dose. MicroRNA expression levels in adult mouse liver were measured using Exiqon miRNA arrays. Our results indicate a distinct lack of effect of BaP of miRNA expression, despite widespread changes in mRNA levels (measured using Agilent arrays). Lack of miRNA changes was confirmed with Agilent miRNA arrays. Keywords: Toxicology, miRNA Adult male B6C3F1 mice were exposed to a daily dose of corn oil (vehicle control group) or 150 mg/kg BaP (treatment group) for 3 d (n=6 per group). Mice were sacrificed at 4 h or 24 h following the last dose and liver lobes were extracted and flash frozen. Exiqon miRNA arrays were used to examine changes in miRNA transcript levels in random liver lobe sections.

2010-10-18 | E-GEOD-18782 | biostudies-arrayexpress

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