Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Maternal inhalation of surface-coated nano-sized titanium dioxide (UV-Titan): Effects in prenatally exposed offspring on hepatic DNA damage and gene expression

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Williams

PROVIDER: E-GEOD-29067 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice: effects in prenatally exposed offspring on hepatic DNA damage and gene expression.

Jackson Petra P Halappanavar Sabina S Hougaard Karin Sørig KS Williams Andrew A Madsen Anne Mette AM Lamson Jacob Stuart JS Andersen Ole O Yauk Carole C Yauk Carole C Wallin Håkan H Vogel Ulla U

Nanotoxicology 20111128 1

We investigated effects of maternal pulmonary exposure to titanium dioxide (UV-Titan) on prenatally exposed offspring. Time-mated mice (C57BL/6BomTac) were inhalation exposed (1 h/day to 42 mg UV-Titan/m(3) aerosolised powder or filtered air) during gestation days (GDs) 8-18. We evaluated DNA strand breaks using the comet assay in bronchoalveolar lavage (BAL) cells and livers of the time-mated mice (5 and 26-27 days after inhalation exposure), and in livers of the offspring (post-natal days (PND ...[more]

PMID: 22117692

Similar Datasets

Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.

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).

Dataset Information

Maternal inhalation of surface-coated nano-sized titanium dioxide (UV-Titan): Effects in prenatally exposed offspring on hepatic DNA damage and gene expression

Publications

Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice: effects in prenatally exposed offspring on hepatic DNA damage and gene expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure