2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) AFFECTS KERATIN-1 AND KERATIN-17 GENE-EXPRESSION AND DIFFERENTIALLY INDUCES KERATINIZATION IN HAIRLESS MOUSE SKIN

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes chloracne in humans by mechanisms that are as yet poorly under stood. Because TCDD is known to affect keratinocyte differentiation in vitro, we have studied TCDD-dependent morphologic changes and the exp ression of murine keratin 1 (MK1; differentiation associated) and kera tin 17 (MK17; presumably hyperproliferation associated) in HRS/J hr/hr hairless mouse skill, TCDD (0.2 mu g in acetone) applied topically to the dorsal skin caused epidermal acanthosis and hyperkeratosis of the dermal cysts as well as an involution of the utricles and the sebaceo us glands, By means of in situ hybridization with digoxigenin-labeled riboprobes of sections from untreated and vehicle (control)-treated sk in, we localized MK1 mRNA to the epidermal spinous cell compartment. M K17 transcripts were detected only in the derivatives of the hair foll icle-utricle epithelium and dermal cysts, No spatial overlap was obser ved between MK1 and MK17 expression. After TCDD application, MK17 was newly expressed in the upper spinous cell layers of the interfollicula r epidermis, although it was suppressed in the involuting utricles, in contrast, MK1 expression in the interfollicular epidermis was not aff ected by TCDD. Furthermore, MK1 expression was induced in the epitheli um of the utricle remnants and in some dermal cysts. These data sugges t that increased keratinization of the part of the follicular epitheli um corresponding to the dermal cyst epithelium of hairless mice most p robably explains the pathogenesis of TCDD-induced chloracne. The resul ts demonstrate, furthermore, that TCDD can differentially affect kerat inocyte differentiation in vivo as well as in vitro.