Linked Life Data

17984292

Source:http://linkedlifedata.com/resource/pubmed/id/17984292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-9
pubmed:abstractText
Technical-grade dichlorodiphenyltrichloroethane (DDT) is an agricultural pesticide and malarial vector control agent that has been designated a potential human hepatocarcinogen. The o,p'-enantiomer exhibits estrogenic activity that has been associated with the carcinogenicity of DDT. The temporal and dose-dependent hepatic estrogenicity of o,p'-DDT was investigated using complementary DNA microarrays in immature ovariectomized Sprague-Dawley rats with complementary histopathology and tissue-level analysis. Animals were gavaged with 300 mg/kg o,p'-DDT either once or once daily for 3 consecutive days. Liver samples were examined 2, 4, 8, 12, 18, or 24 h after a single dose or following three daily doses. For dose-response studies, a single dose of 3, 10, 30, 100, or 300 mg/kg body weight o,p'-DTT was administered for 3 consecutive days. Genes associated with drug metabolism (Cyp2b2 and Cyp3a2), the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), cell proliferation (Ccnd1, Ccnb1, Ccnb2, and Stmn1), and oxidative stress (Gclm and Hmox1) were significantly induced. Cyp2b2 exhibited dose-dependent regulation and was significantly induced across all time points, while cell proliferation- and oxidative stress-related genes exhibited transient induction. The induction of Cyp2b2 and Cyp3a2 mRNA levels suggest PXR/CAR activation, consistent with expression of genes associated with oxidative stress. Few genes known to be estrogen receptor (ER) regulated were differentially expressed when compared to the hepatic gene expression profile elicited by ethynyl estradiol in immature ovariectomized C57BL/6 mice using the same study design and analysis methods. These data indicate that o,p'-DDT elicits PXR/CAR-, not ER-, mediated gene expression in the rat liver. Based on the species-specific differences in CAR regulation, the extrapolation of rodent DDT hepatocarcinogenicity to humans warrants further investigation.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-63
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:17984292-Administration, Oral, pubmed-meshheading:17984292-Animals, pubmed-meshheading:17984292-Carcinogens, Environmental, pubmed-meshheading:17984292-Cell Proliferation, pubmed-meshheading:17984292-DDT, pubmed-meshheading:17984292-Dose-Response Relationship, Drug, pubmed-meshheading:17984292-Female, pubmed-meshheading:17984292-Gene Expression, pubmed-meshheading:17984292-Gene Expression Profiling, pubmed-meshheading:17984292-Liver, pubmed-meshheading:17984292-Mice, pubmed-meshheading:17984292-Mice, Inbred C57BL, pubmed-meshheading:17984292-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17984292-Ovariectomy, pubmed-meshheading:17984292-Rats, pubmed-meshheading:17984292-Rats, Sprague-Dawley, pubmed-meshheading:17984292-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:17984292-Receptors, Estrogen, pubmed-meshheading:17984292-Receptors, Steroid, pubmed-meshheading:17984292-Transcription Factors
pubmed:year
2008
pubmed:articleTitle
o,p'-DDT elicits PXR/CAR-, not ER-, mediated responses in the immature ovariectomized rat liver.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural