The usefulness of toxicogenomics for predicting acute skin irritation on in vitro reconstructed human epidermis.
In vitro models aiming at replacing the traditional animal test for determining the skin irritation potential of a test substance have been developed, evaluated in prevalidation studies and recently validated by the European Center for the Validation of Alternative Methods (ECVAM). To investigate the usefulness of toxicogenomic technologies to identify novel mechanistic endpoints for skin irritation responses, the present work challenged the human reconstituted epidermis model validated by ECVAM with four irritant chemicals and four non-classified chemicals tested at subcytotoxic concentrations. Using a specifically designed low-density DNA array, about 50 genes out of 240 were found to be significantly and differentially expressed between tissues exposed to irritant and non-irritant chemicals for at least one test chemical when compared to the seven others. These genes are involved in cell signalling, stress response, cell cycle, protein metabolism and cell structure. Among them, 16 are expressed in the same way whatever the irritant compound applied. The differential gene expressions might represent new or additional endpoints useful for the mechanistic understanding and perhaps also the hazard assessment of the skin irritation potential of chemicals and products.
Borlon
Céline
C
Research Unit on Cellular Biology (URBC), Department of Biology, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur, Belgium.
Godard
Patrice
P
Eskes
Chantra
C
Hartung
Thomas
T
Zuang
Valérie
V
Toussaint
Olivier
O
D000826:Animal Testing Alternatives / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D017453:Dermatitis, Irritant / Q000209:etiology* / Q000235:genetics; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023422:Skin Irritancy Tests / Q000379:methods*; D043922:Toxicogenetics
D007509:Irritants; D004247:DNA