Dioxin induces transforming growth factor-α in human keratinocytes

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental toxicant, is a tumor promoter that induces hyperplasia in epithelial cells. Exposure of cultured human keratinocytes to TCDD, resulted in a time-dependent dioxin-specific Ah receptor-mediated release of transforming growth factor-α (TGF-α) into the culture medium. Cultures exposed to TCDD showed a rate of TGF-αa secretion into the medium of about 30 fmol/ml/day, as well as a 3- to 6-fold increase in TGF-α mRNA expression. Increased production of TGF-α in human keratinocytes exposed to TCDD demonstrates a modulation of autocrine regulation in those cells. These results suggest that induction of TGF-α could be an important part of the mechanism of dioxin-mediated toxicity and tumor promotion.