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
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.