Transcriptomics

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


ABSTRACT: 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 Agilent’s miRNA complete labelling and Hyb Kit (Agilent Tech, Mississauga, ON, Canada).

ORGANISM(S): Mus musculus  

SUBMITTER: Christine L Lemieux   Andrew Williams  Paul A White  Carole L Yauk  Amal I Malik  Andrea Rowan-Carroll 

PROVIDER: E-GEOD-35195 | ArrayExpress | 2013-07-02

SECONDARY ACCESSION(S): GSE35195PRJNA155965

REPOSITORIES: GEO, ArrayExpress

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Publications

Hepatic genotoxicity and toxicogenomic responses in Muta™Mouse males treated with dibenz[a,h]anthracene.

Malik Amal I AI   Rowan-Carroll Andrea A   Williams Andrew A   Lemieux Christine L CL   Long Alexandra S AS   Arlt Volker M VM   Phillips David H DH   White Paul A PA   Yauk Carole L CL  

Mutagenesis 20130621 5


Dibenz[a,h]anthracene (DB[a,h]A) is a polycyclic aromatic hydrocarbon that is a by-product of combustion and a potent carcinogen. Few studies have investigated the effects of DB[a,h]A on mRNA and microRNA expression to dissect the mechanisms involved in carcinogenesis. In this study, mature male mice (Muta(™)Mouse) were exposed to 6.25, 12.5 and 25mg/kg/day DB[a,h]A by oral gavage for 28 consecutive days. Results were compared with mice similarly exposed to benzo[a]pyrene (B[a]P) in our previous  ...[more]

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