Increased epidermal transglutaminase activity following 2,3,7,8-tetrachlorodibenzo-p-dioxin: in vivo and in vitro studies with mouse skin.

In previous studies it has been shown that topical treatment of hairless mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) induces hyperproliferation and hyperkeratinization in the epidermis of hairless mice. The present investigation demonstrated that such TCDD-induced morphological changes in skin in vivo are accompanied by increased levels in activity of epidermal transglutaminase (ETG), the enzyme associated with terminal epidermal differentiation. Exposure of mouse epidermal cells in tissue culture to 10(-9) M TCDD also resulted in a significant increase in ETG activity, despite the fact that morphologically these cultures (grown at 0.07 mM ionic calcium concentrations) exhibited no signs of terminal differentiation. Thus one mechanism of action of TCDD in inducing cutaneous changes appears to relate to the stimulation of increased ETG levels.