TY - JOUR
T1 - Alterations in the expression of specific epidermal keratin markers in the hairless mouse by the topical application of the tumor promoters 2,3,7,8-tetrachlorodibenzo-p-dioxin and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
AU - Molloy, Christopher J.
AU - Gallo, Michael A.
AU - Laskin, Jeffrey D.
N1 - Funding Information:
This investigation was supported by a grant from the National Institute of Health Sciences (ES-03647) awarded to J.D.L.
PY - 1987/9
Y1 - 1987/9
N2 - The potent toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes chloracne and acts as a tumor promoter in the hairless HRS/J mouse model. In the present study we characterized changes in mouse epidermal keratin expression following a single topical application of TCDD to the skin of hairless (hr/hr) and haired (hr/+) HRS/J mice. Morphologic changes and alterations in keratin biosynthesis following TCDD treatment were compared with those induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Both TPA and TCDD induced dose-dependent epidermal hyperplasia in hr/hr and hr/+ mice and this was associated with altered keratin subunit expression. In hr/hr mice TCDD caused a pattern of keratin expression that was similar to TPA, characterized by a marked decrease in the synthsis of the Mr. 67000 (bask) and 59000 (acidic) keratins that are specific markers for suprabasal differentiation in the epidermis. In addition, the synthesis of an acidic keratin of Mr 48000 and a basic keratin of Mr 62000 was also decreased. Concomitantly, TCDD caused an increase in the synthesis of a basic keratin of Mr 60000 and acidic keratins of Mr. 54000, 52000 and 49000 that are normally observed in proliferating basal cells and primary epidermal cell cultures. In contrast, while TPA induced similar changes in keratinization in both the hr/+ and hr/hr mice, TCDD-induced hyperplasia in hr/+ mice was only associated with changes in keratin synthesis reflecting increased basal cell proliferation. These results demonstrate that a single application of TCDD to the skin alters the normal pattern of epidermal differentiation in the hr/hr mouse. Molecular events influencing the expression of the keratin genes associated with this process may be linked to the strain-and/or species-specific toxicity of TCDD.
AB - The potent toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes chloracne and acts as a tumor promoter in the hairless HRS/J mouse model. In the present study we characterized changes in mouse epidermal keratin expression following a single topical application of TCDD to the skin of hairless (hr/hr) and haired (hr/+) HRS/J mice. Morphologic changes and alterations in keratin biosynthesis following TCDD treatment were compared with those induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Both TPA and TCDD induced dose-dependent epidermal hyperplasia in hr/hr and hr/+ mice and this was associated with altered keratin subunit expression. In hr/hr mice TCDD caused a pattern of keratin expression that was similar to TPA, characterized by a marked decrease in the synthsis of the Mr. 67000 (bask) and 59000 (acidic) keratins that are specific markers for suprabasal differentiation in the epidermis. In addition, the synthesis of an acidic keratin of Mr 48000 and a basic keratin of Mr 62000 was also decreased. Concomitantly, TCDD caused an increase in the synthesis of a basic keratin of Mr 60000 and acidic keratins of Mr. 54000, 52000 and 49000 that are normally observed in proliferating basal cells and primary epidermal cell cultures. In contrast, while TPA induced similar changes in keratinization in both the hr/+ and hr/hr mice, TCDD-induced hyperplasia in hr/+ mice was only associated with changes in keratin synthesis reflecting increased basal cell proliferation. These results demonstrate that a single application of TCDD to the skin alters the normal pattern of epidermal differentiation in the hr/hr mouse. Molecular events influencing the expression of the keratin genes associated with this process may be linked to the strain-and/or species-specific toxicity of TCDD.
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U2 - 10.1093/carcin/8.9.1193
DO - 10.1093/carcin/8.9.1193
M3 - Article
C2 - 2441885
AN - SCOPUS:0023253594
SN - 0143-3334
VL - 8
SP - 1193
EP - 1199
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -