Effects of the chemical irritants anthralin and benzoyl peroxide on mouse skin epithelial cell protein production

The widely used topical agents anthralin and benzoyl peroxide are potent skin irritants. In the mouse skin model these compounds produce hyperplasia nd are effective skin tumor promoters. In the present studies, we have examined the effects of anthralin and benzoyl peroxide on epidermal proteins and compared them with changes produced by the potent phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). All compounds were applied topically to the shaved dorsal skin of mice. Twenty-four hours later skin fragments were pulse-labeled with 35S-methionine to assay total protein production. Anthralin and TPA produced a marked inhibition of protein synthesis when compared to control and benzoyl peroxidetreated skin. When skin was treated with anthralin at a promoting dose (80 }xg, 354 nmole), incorporation of the radiolabel into epidermis was only 22% of control. Promoting doses of TPA (10 }xg, 17 nmole), however, inhibited protein synthesis to 63% of control. Qualitative changes in protein production induced by the chemicals were examined using oneand two-dimensional gel electrophoresis. Using these techniques, we were able to detect over 100 individual proteins from both treated and untreated mouse skin. TPA and anthralin were found to alter the production of at least seven distinct proteins, six of which are keratins. The profile of benzoyl peroxide-treated epidermal proteins, however, resembled those of control skin, suggesting that this chemical promoter may act by a mechanism distinct from TPA and anthralin.