Title: Effects of retinoic acid on the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced differentiation of in vitro cultured human keratinocytes

Auteur(s): Berkens JAM ; Hassing GAM ; Brouwer A ; Blaauwboer BJ ;  ; 

Year: 1994

Journal: Toxic in Vitro

Subject(s): 2,3,7,8-tetrachlorodibenzo-p-dioxin ; TCDD ; polychlorinated ;  ; 

Summary: In order to study the interactive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzefurans (PCDFs) and retinoic acide onterminal differentiations of primary cultured keratinocytes derived from human foreskins, the amoutn of [35S]methionine-labelled priteins incorporated into cross-linked envelopes (CLEs) was determined. After isolation of the CLEs with sodium dedecyl sulfate, the amount of radioactivity collected on a filter was considered as a quantitative parameter for keratinocyte differentiation. Treatment of keratinocytes with different concentrations of TCDD resulted in a dose-dependent increase in differentiation, while only a minor decrease in differentiation occured after treatment with retinoic acid. However, simultaneous application of 10-8 M TCDD and different concentrations of retinoic acid lid to a dose-dependent decrease in CLE formation. PCDFs exerted an effect on CLE formation similar to that of TCDD but with different potencies. We conclude that (1) TCDD induces a dose-dependent induction of human keratinocyte differentiation, (2) retinoic acid is a potent antagonist of TCDD-induced keratinocyte differentiation, and (3) primary cultures of human keratinocytes can serve as a useful model system to study the interactive effects of xenobiotics and hormone-like substances on the regulation of differentiation.