Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Williams

PROVIDER: E-GEOD-35718 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Subchronic oral exposure to benzo(a)pyrene leads to distinct transcriptomic changes in the lungs that are related to carcinogenesis.

Labib Sarah S Yauk Carole C Yauk Carole C Williams Andrew A Arlt Volker M VM Phillips David H DH White Paul A PA Halappanavar Sabina S

Toxicological sciences : an official journal of the Society of Toxicology 20120518 1

We have previously shown that acute oral exposure to the environmental carcinogen benzo(a)pyrene (BaP) elicits comparable levels of DNA adducts, but distinct transcriptomic changes, in mouse lungs and livers, the two main BaP bioactivating organs. Oral BaP exposure is predominantly associated with lung cancer and not hepatic cancer in some animal models, suggesting that gene expression differences may provide insight into the drivers of tissue-specific carcinogenesis. In the present study, we ex ...[more]

PMID: 22610609

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Project description:Polycyclic aromatic hydrocarbons (PAHs) are widely distributed, carcinogenic environmental contaminants produced as a consequence of the incomplete combustion of fossil fuels. Benzo[a]pyrene (BaP) is a very extensively studied prototypical PAH. We recently reported a complete lack of change in microRNA (miRNA) expression in adult mouse liver following oral gavage with BaP despite a robust transcriptome response. We hypothesized that hepatic miRNAs may not be highly responsive to the treatment. Here, we analyse the pulmonary mRNA and miRNA response to BaP in the same mice. Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Acute exposure to BaP resulted in modest decreases in serum inorganic phosphorous, calcium, glucose, alkaline phosphatase and lactate dehydrogenase in animals treated with 300 mg/kg BaP. 32P postlabeling of DNA revealed similar increases in BaP-DNA adducts in both lungs and livers of exposed mice in a dose dependent manner at the 4 hour time point. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. Over 1,000 genes were statistically differentially expressed (fold change > 1.5 and p < 0.05), encompassing numerous pathways including: oxidative stress, xenobiotic metabolism, cell proliferation, cell cycle, B and T-cell receptor signalling and primary immunodeficiency signalling pathways. Analysis of miRNA profiles revealed downregulation of miR-150, miR-142-5p, 142-3p and upregulation of miR-34c and miR-29b. These miRNAs are involved in various biological processes including immune response, cell proliferation and cell cycle, which are also the main pathways affected at the gene expression level. As BaP exposure does not result in hepatocarcinogenicity, but does cause lung cancer, these miRNAs may play an important role in the outcome of the exposure and be more predictive of carcinogenesis. Keywords: mRNA, miRNA, Pulmonary, non-target tissue, Toxicogenomics, Benzoapyrene Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. This submission only contains the 4hr time point, at control, 150mg/kg and 300mg/kg (except for the liver study where only the control and 300mg/kg samples were used).

Project description:In the present study we investigate the effect of maternal pulmonary exposure to titanium dioxide (UV-Titan designed for use in the paint and lacquer industry) on prenatally exposed offspring. Time-mated mice (C57BL/6BomTac) were exposed by inhalation for 1 h/day to 42 mg UV-titan/m3 aerosolized powder or filtered air during gestation days (GD) 8-18. We evaluated levels of DNA strand breaks using the comet assay in bronchioalveolar lavage (BAL) cells and liver cells of the time-mated mice, and in liver cells of the offspring. In parallel, we analyzed changes in gene expression in the liver tissue of offspring using DNA microarrays. We demonstrate that UV-Titan did not induce DNA strand breaks in the time-mated mice or their offspring. Transcriptional profiling of newborn liver tissue revealed changes in the expression of genes related to the retinoic acid (RA) signalling pathway in the females, while gene expression in male offspring was relatively unaffected by exposure. Time-mated, nulliparous mice (C57BL/6BomTac, Taconic Europe, Ejby, Denmark) were exposed to filtered clean air or approximately 42 mg/m3 UV-Titan on GD 8M-bM-^@M-^S18 for 1 hr/day by a whole-body exposure.Delivery was expected on GD 20, and designated postnatal day (PND) 0. On PND 2, one offspring (M-bM-^@M-^\newbornM-bM-^@M-^]) per litter was killed by decapitation, to yield litters with at least 5 offspring per exposure group. The newborn offspring were collected two days after birth. On PND 23-24 (M-bM-^@M-^\at weaningM-bM-^@M-^]) one male and one female per litter were killed. Organs were dissected, weighed, placed in NUNC cryotubes, snap frozen in liquid N2 and stored at -80M-BM-0C until analysis. Exposed dams were killed on PND 24-25 (26-27 days after last exposure). DNA strad break detection was carried out in bronchoalveolar lavage fluid in dams by COMET assay. Total RNA was extracted from offspring livers and gene expression profiling was carried out on whole liver tissues from offspring. 9 UV-Titan treated and 7 controls mice consisting of 8 males and 8 females mRNA, hepatic, developmental, Toxicogenomics, nano-titanium dioxide

Dataset Information

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

Publications

Subchronic oral exposure to benzo(a)pyrene leads to distinct transcriptomic changes in the lungs that are related to carcinogenesis.

Similar Datasets

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