2,3,7,8-Tetrachlorodibenzo-p-dioxin alters retinoic acid receptor function in human keratinocytes

Kevin L. Lorick, Diane L. Toscano, William A. Toscano

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on all-trans-retinoic acid (trans-RA) binding to retinoic acid receptors (RARs) in cultured human keratinocytes (SCC-12F) was investigated. TCDD and trans-RA elicited opposing actions on the production of biologically active TGF-β. TCDD exposure caused concentration- and time-dependent decreases in trans-RA binding to SCC-12F RARs. The apparent half-maximal effective TCDD concentration = 1 nM. TCDD exerts its action via the aryl hydrocarbon receptor (AhR). TCDBF, a partial AhR agonist, reduced trans-RA binding, indicating AhR involvement (control = 0.33; TCDBF = 0.22; TCDD = 0.142 pmol trans-RA bound/mg nuclear protein). The dissociation constant (Kd) calculated from Eadie-Hofstee analysis of equilibrium binding for trans-RA was 0.13 nM in both TCDD-exposed and control cultures. Approximately half of the trans-RA binding sites were lost in TCDD-exposed cells (control = 0.195; TCDD = 0.108 pmol trans-RA bound/mg protein). The data suggest TCDD may exert its toxic action in human keratinocytes by directly modulating RAR action.

Original languageEnglish (US)
Pages (from-to)749-752
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume243
Issue number3
DOIs
StatePublished - Feb 24 1998

Bibliographical note

Funding Information:
1This work was supported by a grant from the National Institutes of Health, ES-02866.

Fingerprint Dive into the research topics of '2,3,7,8-Tetrachlorodibenzo-p-dioxin alters retinoic acid receptor function in human keratinocytes'. Together they form a unique fingerprint.

Cite this