Linked Life Data

15800033

Source:http://linkedlifedata.com/resource/pubmed/id/15800033

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-5-18
pubmed:abstractText
In an effort to further characterize the mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated toxicity, comprehensive temporal and dose-response microarray analyses were performed on hepatic tissue from immature ovariectomized C57BL/6 mice treated with TCDD. For temporal analysis, mice were gavaged with 30 microg/kg of TCDD or vehicle and sacrificed after 2, 4, 8, 12, 18, 24, 72, or 168 h. Dose-response mice were gavaged with 0, 0.001, 0.01, 0.1, 1, 10, 100, or 300 microg/kg of TCDD and sacrificed after 24 h. Hepatic gene expression profiles were monitored using custom cDNA microarrays containing 13,362 cDNA clones. Gene expression analysis identified 443 and 315 features which exhibited a significant change at one or more doses or time points, respectively, as determined using an empirical Bayes approach. Functional gene annotation extracted from public databases associated gene expression changes with physiological processes such as oxidative stress and metabolism, differentiation, apoptosis, gluconeogenesis, and fatty acid uptake and metabolism. Complementary histopathology (H&E and Oil Red O stains), clinical chemistry (i.e., alanine aminotransferase [ALT], triglyceride [TG], free fatty acids [FFA], cholesterol) and high-resolution gas chromatography/mass spectrometry assessment of hepatic TCDD levels were also performed in order to phenotypically anchor changes in gene expression to physiological end points. Collectively, the data support a proposed mechanism for TCDD-mediated hepatotoxicity, including fatty liver, which involves mobilization of peripheral fat and inappropriate increases in hepatic uptake of fatty acids.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1048-63
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:15800033-Alanine Transaminase, pubmed-meshheading:15800033-Animals, pubmed-meshheading:15800033-Cell Differentiation, pubmed-meshheading:15800033-Cholesterol, pubmed-meshheading:15800033-Dose-Response Relationship, Drug, pubmed-meshheading:15800033-Drug-Induced Liver Injury, pubmed-meshheading:15800033-Environmental Pollutants, pubmed-meshheading:15800033-Fatty Acids, pubmed-meshheading:15800033-Fatty Acids, Nonesterified, pubmed-meshheading:15800033-Female, pubmed-meshheading:15800033-Gene Expression, pubmed-meshheading:15800033-Immunity, Cellular, pubmed-meshheading:15800033-Liver, pubmed-meshheading:15800033-Liver Neoplasms, pubmed-meshheading:15800033-Mice, pubmed-meshheading:15800033-Mice, Inbred C57BL, pubmed-meshheading:15800033-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15800033-RNA, pubmed-meshheading:15800033-Receptors, Aryl Hydrocarbon, pubmed-meshheading:15800033-Tetrachlorodibenzodioxin, pubmed-meshheading:15800033-Time Factors, pubmed-meshheading:15800033-Triglycerides
pubmed:year
2005
pubmed:articleTitle
Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing Michigan 48824-1319, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural