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Science 22 March 1985:
Vol. 227. no. 4693, pp. 1499 - 1502
DOI: 10.1126/science.3856321
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Articles

Science, Vol 227, Issue 4693, 1499-1502
Copyright © 1985 by American Association for the Advancement of Science

articles

Control of cytochrome P1-450 gene expression by dioxin

PB Jones, DR Galeazzi, JM Fisher, and JP Whitlock Jr

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.


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