THE COLIPA SKIN METABOLISM PROJECT: DO IN VITRO ALTERNATIVES COMPRISE ADEQUATE DETOXIFICATION CAPACITIES FOR CHEMICAL TESTING IN SKIN?

• TR Number: 605
• Keywords: CYP1, CYP1A, CYP1B1, CYP2, CYP2BPROD, CYP2E1, CYP3A, Cytochrome P450, EPI-200, EROD, Glutathione S-Transferase GST, HaCaT, Human skin, MROD, Minipig, Mouse, N-Acetyltransferase NAT, NCTC 2544 cell line, NHEK, Phase I detoxification enzymes, Phase II detoxification enzymes, Rat Aroclor, UDP-Glucuronosyl-transferase

Background: The aim of this study is to characterize the specific enzymatic activity of Phase I and II detoxification enzymes in human ex vivo skin compared to skin cell-derived in vitro models. Emphasis was here put on the determination of basal enzyme activity. Conclusions: Basal CYP1A, 1B1 and CYP2B activity is below detection limit in human skin microsomes and skin equivalents, but in-ducible. CYP3A is present at basal level, but was not inducible in this setup. Phase II enzymes are far more prominent in skin than Phase I CYP enzymes. Phase II activity is not dependent on donor, but shows slight activity decrease depending on cultivation time. Phase II enzymes were not inducible in this setup by the model genotoxin 3-Methylcholantrene. Phase II: 3-D models (EPI-200) resemble skin metabolism well.