Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin model. Development of the SENS-IS assay.
Analysis of genes modulated during the sensitization process either on mice (LLNA) or human (blisters) combined with data mining has allowed the definition of a comprehensive panel of sensitization biomarkers. This set of genes includes already identified markers such as the ARE family and others not yet associated with the sensitization process (the so-called SENS-IS gene subset). The expression of this set of genes has been measured on reconstituted human epidermis models (Episkin) exposed to various sensitizers and non-sensitizers. Fine analysis of their expression pattern indicates that it is the number of modulated genes rather than the intensity of up-regulation that correlates best with the sensitization potential of a chemical. Moreover, sensitizers that are weak inductors of ARE genes tend to be relevant modulators of the SENS-IS subset. By combining the expression data obtained with both gene subsets, it is now possible to identify a wide variety of sensitizers on a test system (in vitro reconstructed human epidermis) that is very similar to the in vivo situation and compatible with a large variety of test substance characteristics.
ImmunoSearch, Les Cyclades, Chemin de Camperousse, Grasse, France.
Françoise
F
Cottrez
ImmunoSearch, Les Cyclades, Chemin de Camperousse, Grasse, France.
Elodie
E
Boitel
ImmunoSearch, Les Cyclades, Chemin de Camperousse, Grasse, France.
Claude
C
Auriault
ImmunoSearch, Les Cyclades, Chemin de Camperousse, Grasse, France.
Pierre
P
Aeby
ImmunoSearch, Les Cyclades, Chemin de Camperousse, Grasse, France. Electronic address: hgroux@immunosearch.fr.
Hervé
H
Groux
D000826:Animal Testing Alternatives; D000818:Animals; D015415:Biomarkers; D003545:Cysteine / Q000737:chemistry; D004817:Epidermis / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005819:Genetic Markers; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D051379:Mice; D012867:Skin / Q000187:drug effects*; D023422:Skin Irritancy Tests / Q000379:methods*; D043922:Toxicogenetics
D015415:Biomarkers; D005819:Genetic Markers; D007509:Irritants; D003545:Cysteine
Alternatives to animal tests; Reconstituted epidermis; SENS-IS; Skin sensitization; Toxicogenomics