2,3,7,8-Tetrachlorodibenzo-p-dioxin induces hyperplasia in confluent cultures of human keratinocytes

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototype for a group of halogenated aromatic hydrocarbons which can be potent modulators of growth and differentiation of epithelial tissues. TCDD causes chloracne and can act as a skin tumor promoter, but these actions have been demonstrated only in animals in which TCDD causes epidermal hyperplasia. Study of the hyperplastic response to TCDD has been hampered by lack of an in vitro model; all previous investigations indicated that TCDD had no in vitro effect on cell growth. We show here that nanomolar concentrations of TCDD cause hyperplasia in confluent cultures of human keratinocytes and suggest that this model system will be useful for analyzing mechanisms of TCDD-induced epithelial hyperplasia and genetic differences in responsiveness to TCDD.