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Toxicol In Vitro ; 27(8): 2213-24, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23999411

RESUMEN

Recent changes in regulatory requirements and social views on animal testing have accelerated the development of reliable alternative tests for predicting skin sensitizing potential of chemicals. In this study, we aimed to develop a new in vitro skin sensitization assay using reconstructed human epidermis, RhE model, which is expected to have broader applicability domain rather than existing in vitro assays. Microarray analysis revealed that the expression of five genes (ATF3, DNAJB4, GCLM, HSPA6 and HSPH1) related to cellular stress response were significantly up-regulated in RhE model after 6h treatment with representative skin sensitizers, 1-fluoro-2,4-dinitrobenzene and oxazolone, but not a non-sensitizer, benzalkonium chloride. The predictive performance of five genes was examined with eight skin sensitizers (e.g., cinnamic aldehyde), four non-sensitizers (e.g., sodium lauryl sulfate) and four pre-/pro-haptens (e.g., p-phenylenediamine, isoeugenol). When the positive criteria were set to obtain the highest accuracy with the animal testing (LLNA), ATF3, DNAJB4 and GCLM exhibited a high predictive accuracy (100%, 93.8% and 87.5%, respectively). All tested pre-/pro-haptens were correctly predicted by both ATF3 and DNAJB4. These results suggested that the RhE-based assay, termed epidermal sensitization assay (EpiSensA), could be an useful skin sensitization assay with a broad applicability domain including pre-/pro-haptens.


Asunto(s)
Alérgenos/toxicidad , Perfilación de la Expresión Génica , Haptenos/toxicidad , Pruebas de Irritación de la Piel , Alternativas a las Pruebas en Animales , Compuestos de Benzalconio/toxicidad , Dinitrofluorobenceno/toxicidad , Epidermis , Humanos , Técnicas In Vitro , Análisis de Secuencia por Matrices de Oligonucleótidos , Oxazolona/toxicidad
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