Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro
| Autor: | Tzutzuy Ramirez, E. Fabian, Robert Landsiedel, V. Blatz, B. van Ravenzwaay, D. Vogel, Tobias Eltze, Franz Oesch, Susanne N. Kolle |
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| Rok vydání: | 2013 |
| Předmět: |
Animal Use Alternatives
Keratinocytes Male Arylamine N-Acetyltransferase Health Toxicology and Mutagenesis Metabolite Aldehyde dehydrogenase Cosmetics Toxicology Esterase Cell Line Xenobiotics chemistry.chemical_compound Cytosol Limit of Detection Microsomes Toxicity Tests Animals Humans Rats Wistar Skin Alcohol dehydrogenase biology Acetylation Dendritic Cells General Medicine Monooxygenase In vitro Rats Isoenzymes chemistry Biochemistry Cell culture Dermatitis Allergic Contact Microsomes Liver biology.protein |
| Zdroj: | Archives of Toxicology. 87:1683-1696 |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities. |
| Databáze: | OpenAIRE |
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