EFFECTS OF RETINOIC ACID ON THE 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED DIFFERENTIATION OF IN-VITRO CULTURED HUMAN KERATINOCYTES

Citation
Jam. Berkers et al., EFFECTS OF RETINOIC ACID ON THE 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED DIFFERENTIATION OF IN-VITRO CULTURED HUMAN KERATINOCYTES, Toxicology in vitro, 8(4), 1994, pp. 605-608
Citations number
10
Categorie Soggetti
Toxicology
Journal title
ISSN journal
08872333
Volume
8
Issue
4
Year of publication
1994
Pages
605 - 608
Database
ISI
SICI code
0887-2333(1994)8:4<605:EORAOT>2.0.ZU;2-I
Abstract
In order to study the interactive effects of 2,3,7,8-tetrachlorodibenz o-p-dioxin (TCDD), polychlorinated dibenzofurans (PCDFs) and retinoic acid on terminal differentiation of primary cultured keratinocytes der ived from human foreskins, the amount of [S-35]methionine-labelled pro teins incorporated into cross-linked envelopes (CLEs) was determined. After isolation of the CLEs with sodium dodecyl 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 in crease in differentiation, while only a minor decrease in differentiat ion occurred after treatment with retinoic acid. However, simultaneous application of 10(-8) TCDD and different concentrations of retinoic a cid led to a dose-dependent decrease in CLE formation. PCDFs exerted a n effect on CLE formation similar to that of TCDD but with different p otencies. 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) prima ry cultures of human keratinocytes can serve as a useful model system to study the interactive effects of xenobiotics and hormone-like subst ances on the regulation of differentiation.