LuSens: Shedding light on skin sensitization

Abstract

Skin sensitizers or their metabolites are predominantly electrophilic molecules and have the capacity to induce the Nrf2 signalling pathway. Therefore, they trigger the expression of genes under the control of the antioxidant response element (ARE), most of which are detoxifying enzymes and other protective proteins. In the meantime extensive evidence is available to demonstrate that the activation of the Nrf2 pathway provides valuable information for identification of skin sensitizers. The activation of keratinocytes is the second key event of skin sensitization adverse outcome pathway described by the OECD, and the LuSens assay is used to generate information to cover this key event. The LuSens assay is based on a human keratinocyte reporter cell line harbouring the ARE of the NADPH:quinone oxidoreductase 1 (nqo1) gene from the rat and the reporter gene of luciferase. In the presence of skin sensitizers, luciferase is overexpressed indicating direct activation of the nqo1-ARE. The LuSens assay has demonstrated good proficiency to detect skin sensitizers, good reproducibility, as well as its interchangeability with the KeratinoSens™ assay. Moreover, studies have also demonstrated its use as part of a testing battery, resulting in accuracy similar to that obtained with the in vivo gold standard, the local lymph node assay. In this context, the LuSens assay is a major contribution to the replacement of in vivo experiments for skin sensitization.