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.
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.
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).
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. Individual total RNA (200 ng) from 4-5 mice per treatment group (control, 6.25 mg/kg, 12.5mg/kg, and 25mg/kg) and universal reference total RNA (Stratagene, Mississauga, ON, Canada) was used to synthesize double stranded cDNA. Agilent mouse 8 x 60 K oligonucleotide microarrays were used to assess global gene expression in response to 6.25, 12.50, and 25 mg/kg DB[a,h]A treatment
Project description:This SuperSeries is composed of the following subset Series: GSE24907: Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (gene expression) GSE24909: Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (miRNA) Refer to individual Series
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
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).
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