Regulation of epidermal growth factor binding in a human keratinocyte cell line by 2,3,7,8-tetrachlorodibenzo-p-dioxin

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

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) decreased the binding of epidermal growth factor (EGF) by the human keratinocyte cell line SCC-12F. This response was concentration dependent (half-maximal effective concentration, EC50 = 1.8 nm) and stereospecific. Scatchard analysis of EGF binding indicated that treatment with TCDD resulted in a loss of high-affinity (Kd = 0.28 nm) binding sites. This loss was accompanied by a concomitant inhibition of EGF-stimulated DNA synthesis. The kinetics for the decrease of EGF binding by TCDD and benzo[a]pyrene (BP) were compared. Inhibition of EGF binding by BP was maximal by 24 hr, with 90% recovery of EGF binding apparent by 48 hr. In contrast, TCDD treatment for 72 hr was required to produce maximal inhibition, and no recovery was evident up to 10 day after removal of TCDD from the growth medium. The data indicate that modulation of EGF binding by TCDD was mediated by the Ah receptor. Subsequent cellular responses, for example, inhibition of EGF-stimulated DNA synthesis, may be important in the expression of altered differentiation patterns observed in human epidermal keratinocytes exposed to TCDD.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Feb 1985

Bibliographical note

Funding Information:
’ This work was presented at the 74th Annual Meeting of the American Society of Biological Chemists, 1983. This research was supported by Grants ES-02866 and a Pilot Project from Center Grant 5P30ES00002 from the National Institute of Environmental Health Sciences. W.A.T. is supported by funds from the Mellon Foundation. ’ Chemical Industry Institute of Toxicology Predoctoral Fellow. 3 Abbreviations used: AHH, arylhydrocarbon hydroxylase; BP, benzo[a]pyrene; BSA, bovine serum albumin; DMEM, Dulbecco’s modified Eagle’s medium; MezSO, dimethyl sulfoxide; 2,7DpD, 2,7dichlorodibenzo-p dioxin; EC50, half-maximal effective concentration; EGF,

Copyright 2014 Elsevier B.V., All rights reserved.


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