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Control of Cytochrome P$_{1}$-450 Gene Expression by Dioxin

Phillip B. C. Jones, Donna R. Galeazzi, Joan M. Fisher and James P. Whitlock
Science
New Series, Vol. 227, No. 4693 (Mar. 22, 1985), pp. 1499-1502
Stable URL: http://www.jstor.org/stable/1694978
Page Count: 4
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Control of Cytochrome P$_{1}$-450 Gene Expression by Dioxin
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Abstract

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 P$_{1}$-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$\prime $ end of the cytochrome P$_{1}$-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 P$_{1}$-450 gene is under both positive and negative control by at least two trans-acting regulatory factors.

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