Publication Date:
1985-03-22
Description:
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may produce its effects by altering gene expression in susceptible cells. In mouse hepatoma cells, TCDD induces the transcription of the cytochrome P1-450 gene, whose product, aryl hydrocarbon hydroxylase, contributes both to the detoxification and to the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons. A DNA fragment containing sequences flanking the 5' end of the cytochrome P1-450 gene was isolated and analyzed. This DNA fragment contains a cis-acting control element with at least three functional domains: a putative promoter, an inhibitory domain upstream from the promoter that blocks its function, and a TCDD-responsive domain still farther (1265 to 1535 base pairs) upstream of the promoter. These findings, together with results from earlier studies, imply that transcription of the cytochrome P1-450 gene is under both positive and negative control by at least two trans-acting regulatory factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, P B -- Galeazzi, D R -- Fisher, J M -- Whitlock, J P Jr -- CA09302/CA/NCI NIH HHS/ -- CA32786/CA/NCI NIH HHS/ -- GM07149/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1985 Mar 22;227(4693):1499-502.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3856321" target="_blank"〉PubMed〈/a〉
Keywords:
Acetyltransferases/biosynthesis/genetics
;
Animals
;
Cell Line
;
Chloramphenicol O-Acetyltransferase
;
Cytochrome P-450 Enzyme System/*genetics
;
DNA, Recombinant
;
Dioxins/*pharmacology
;
Enzyme Induction
;
Gene Expression Regulation/*drug effects
;
*Genes, Regulator
;
Liver Neoplasms, Experimental
;
Mice
;
*Promoter Regions, Genetic
;
Tetrachlorodibenzodioxin/*pharmacology
;
Transcription Factors/metabolism
;
Transcription, Genetic/drug effects
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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