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J. Biol. Chem., Vol. 266, Issue 15, 9591-9597, May, 1991
EJ Choi, DG Toscano, JA Ryan, N Riedel and WA Toscano Jr
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-alpha (TGF-alpha) into the culture medium. Cultures exposed
to TCDD showed a rate of TGF-alpha secretion into the medium of about 30
fmol/ml/day, as well as a 3- to 6-fold increase in TGF-alpha mRNA
expression. Increased production of TGF-alpha in human keratinocytes
exposed to TCDD demonstrates a modulation of autocrine regulation in those
cells. These results suggest that induction of TGF- alpha could be an
important part of the mechanism of dioxin-mediated toxicity and tumor
promotion.
Dioxin induces transforming growth factor-alpha in human keratinocytes
Division of Environmental and Occupational Health, University of Minnesota, Minneapolis 55455.
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