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NAD(P)H:QUINONE REDUCTASE ACTIVITY IN HUMAN EPIDERMAL KERATINOCYTES AND RECONSTRUCTED EPIDERMAL MODELS.

Harris, I.R., Siefken, W., Beck-Oldach, K., Wittern, K.P., Pollet, D. Paul Gerson Unna-Skin Research Center, Beiersdorf AG, Hamburg, Germany.
Abstract

Reconstructed epidermal models may provide a suitable and relevant model for screening compounds such as quinones, which affect the activities of phase I and II enzymes involved in epidermal detoxification. Reconstructed epidermis may also allow the study of the metabolism of topically applied compounds by the phase I and II enzymes. We demonstrate that NAD(P)H:quinone reductase (NQR) activity is present in three different types of reconstructed epidermal models and that levels vary depending on the type of model. We also determined the inter- and intrabatch variability and demonstrate that NQR activity can be significantly inhibited by dicumarol treatment. The NQR activity in reconstructed epidermis is similar to that in human epidermis and lower than in cultured keratinocytes. Therefore reconstructed epidermis is a more suitable model for testing the effects of topically applied compounds on NQR activity or the metabolism of the compound by NQR.

Keywords

Compound screening, Detoxification, Dicumarol, Enzyme activity, EpiDerm, Epidermal detoxification, Inter-batch variability, Intra-batch variability, Keratinocyte, Menadione, Metabolism, NAD(P)H:quinone reductase (NQR), NQR, NQR activity, Nitro compounds, Phase I enzyme, Phase II enzyme, Quinone reductase, Reconstructed epidermal model, Reconstructed epidermis, Reconstructed skin, Topically applied compound, Vitamin K3, Xenobiotics

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