Induction of 7-ethoxycoumarin O-deethylase activity in cultured human epithelial cells by 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD): Evidence for TCDD receptor

Laurie G. Hudson, Rashid Shaikh, William A. Toscano, William F. Greenlee

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42 Scopus citations

Abstract

The responsiveness of 5 human squamous cell carcinoma (SCC)1 lines derived from tumors of the epidermis and tongue to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was assessed by measuring the induction of the cytochrome P1-450-mediated monooxygenase activity, 7-ethoxycoumarin O-deethylase (ECOD). In 4 of the SCC lines the EC502 for this response was approximately 10-9M, whereas in one line the EC50 was 10-10M. In each of the less sensitive lines a concentration of 10-10M TCDD elicited less than 5% of the maximal enzyme activity. Specific binding of radiolabeled TCDD was detected in the cytosol fraction from all the SCC lines. The relative amount of receptor measured in each line correlated with maximally-induced ECOD activity. The data indicate that human cell lines derived from a target tissue for TCDD toxicity contain the TCDD receptor and show differential sensitivity to TCDD analogous to the murine strain differences in sensitivity regulated by the Ah locus.

Original languageEnglish (US)
Pages (from-to)611-617
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume115
Issue number2
DOIs
StatePublished - Sep 15 1983

Bibliographical note

Funding Information:
This research was supported in part by NIH Grant ES-02866 and ErA Grant CR80780R (RS). LGH was a recipient of Burroughs-Wellcome Foundation and Chemical Industry Institute of Toxicology Predoctoral Fellowships.

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