Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system.

摘要: Reporter cell lines are a particularly useful tool to screen for the skin sensitization potential of chemicals. Current models based on Keap1-Nrf2 mimic induction by conducting antioxidant response element-luciferase plasmids. However, plasmid-based reporters may ignore comprehensive aspects induction, thus affecting accuracy hazard identification. Herein, we developed novel HaCaT-based reporter system, EndoSens, whereby luciferase was specifically inserted into cassette heme oxygenase (decycling) 1 (HMOX1, most consistent marker induced sensitizers) CRISPR/Cas9. Testing data from 20 coded substances showed an 90%, sensitivity 91.7%, and specificity 87.5%, which exceeded OECD requirement. Among 35 chemicals examined, predictivity better than reported validated KeratinoSens™. These results indicate that EndoSens assay could advance sensitization, making it promising in vitro testing.