INVESTIGATION OF THE BIOTRANSFORMING CAPACITY OF HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

• TR Number: 678
• Keywords: Alcohol- Dehydrogenases (ADH), Aldehyde-Dehydrogenases (ALDH), Biotransformation, DNA repair, EpiDermFT™, EpiDerm™, EpiDerm™FT, Ex-vivo human skin, Flavin-dependent monoxygenases (FMO), KerationoSens cell line, Metabolic capacity, Metabolic competence, Monolayer, N-Acetyltransferases (NAT), Phenion®FT, Tuchrome P450 (CYP), UDP-Glucuronyltransferases (UDP-GT)

Skin penetration is a route of xenobiotic uptake in the body, however, less information is available about the fate of the penetrated xenobiotic in regard of metabolic turn over. The presence of xenobiotic metabolizing enzymes in skin has previously been shown by transcriptional expression analysis including CYPs, Flavin-dependent monooxygenases (FMO), Alcohol- (ADH) and Aldehyde-Dehydrogenases (ALDH), N- Acetyltransferases (NAT) and UDP-Glucuronyltransferases (UDP-GT) [1-4]. However, the catalytic activity in skin tissue was rarely specified. Human reconstructed skin models are under investigation to be used as in vitro alternative for in vivo animal testing. As metabolic processing is required for several xenobiotic-induced effects, i.e. genotoxicity, characterization of enzyme activities of in vitro skin models in comparison to native skin is required for their usage in toxicity testing.