| Autor: |
Zhong, Guorui, Li, Haojian, Bai, Jing, Pang, Shihui, He, Changsheng, Du, Xinyi, Wang, Haijie, Zhang, Qixiao, Xie, Shuilin, Du, Hongli, Dai, Renke, Huang, Lizhen |
| Předmět: |
|
| Zdroj: |
Archives of Toxicology; Oct2018, Vol. 92 Issue 10, p3103-3115, 13p, 3 Charts, 6 Graphs |
| Abstrakt: |
Reporter cell lines are a particularly useful tool to screen for the skin sensitization potential of chemicals. Current cell models based on Keap1-Nrf2 mimic induction by conducting antioxidant response element-luciferase plasmids. However, plasmid-based reporters may ignore comprehensive aspects of induction, thus affecting the accuracy of hazard identification. Herein, we developed a novel HaCaT-based reporter system, EndoSens, whereby luciferase was specifically inserted into the cassette for heme oxygenase (decycling) 1 (HMOX1, the most consistent marker induced by skin sensitizers) by CRISPR/Cas9. Testing data from 20 coded substances showed an accuracy of 90%, sensitivity of 91.7%, and specificity of 87.5%, which exceeded the OECD requirement. Among the 35 chemicals examined, predictivity was better than reported for the validated KeratinoSens™. These results indicate that the EndoSens assay could advance the predictivity of skin sensitization, thus making it a promising tool for in vitro skin sensitization testing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink