Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse lung tissue after exposure to mainstream tobacco smoke

ABSTRACT: We have examined the impact of subchronic levels of tobacoo smoke on murine lungs. We have used high density DNA microarray and analysed lung tissues from mice exposed to mainstream tobacco smoke (MTS). Our results reveal induction of inflammatory cytokine interleukin-6 (IL-6) and its antagonist suppressor of cytokine signalling (SOCS3) mRNA in smoking group. We also show that these changes are transient and are reversed completely after a period of cessation of smoking. Experiment Overall Design: Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or six weeks following the last cigarette. Left lung lobes were removed and flash frozen. Total RNA was isolated from a small part of the frozen lung and was hybridized against universal mouse reference RNA to Agilent Oligo DNA microarrays (Agilent Technologies) containing 22,000 transcripts. Microarrays were normalized using a global LOWESS approach and analyzed by MAANOVA 2.0 and SAM. Microarray results were validated by real time RT-PCR. Impact of alteration in expression of select genes was further validated by analysing their total protein levels in lung tissue homogenates.

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Williams

PROVIDER: E-GEOD-12930 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke.

Halappanavar Sabina S Russell Marsha M Stampfli Martin R MR Williams Andrew A Yauk Carole L CL Yauk Carole L CL

BMC medical genomics 20090821

<h4>Background</h4>Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated.<h4>Methods</h4>Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks ...[more]

PMID: 19698101

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Project description:Genomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant?s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.

Dataset Information

Transcription profiling of mouse lung tissue after exposure to mainstream tobacco smoke

Publications

Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke.

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