Comparison of Glutathione S-Transferase and Cytochrome P-450 IA1 Activities in Cultured Keratinocytes and Reconstructed Epidermal Models

January 2002 in “ Skin Pharmacology and Physiology ”

Ian R. Harris, Wilfried Siefken, Konstanze Beck-Oldach, Michael R. Brandt, Klaus‐Peter Wittern, Dieter Pollet

glutathione S-transferase cytochrome P450 IA1 keratinocytes reconstructed epidermal models human epidermis hair follicles EROD activity 3-methylcholanthrene β-naphthoflavone clotrimazole ECOD activity xenobiotic metabolism GST P450 skin models 3-MC beta-naphthoflavone

TLDR Reconstructed skin models are useful for studying how skin processes certain chemicals.

This study evaluated the activities of phase I enzyme cytochrome P450 IA1 and phase II enzyme glutathione S-transferase (GST) in cultured keratinocytes, reconstructed epidermal models, and human epidermis or hair follicles. EROD activity, a measure of cytochrome P450 IA1, was present in cultured keratinocytes and could be induced by 3-methylcholanthrene (3-MC) and β-naphthoflavone, with induction levels increasing with cell confluence. Clotrimazole inhibited induced EROD activity in a dose-dependent manner. EROD activity was not detected in hair follicles or untreated epidermal models but could be induced by 3-MC, with induction varying by batch. ECOD activity mirrored EROD activity. GST activity was found in all samples, with levels in reconstructed models equal to or higher than those in epidermal samples. The findings suggested that reconstructed skin models could be valuable for studying the effects of non-water-soluble topical formulations on xenobiotic metabolism.

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