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

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...

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Bibliographic Details
Published in:Archives of toxicology 2018-10, Vol.92 (10), p.3103-3115
Main Authors: Zhong, Guorui, Li, Haojian, Bai, Jing, Pang, Shihui, He, Changsheng, Du, Xinyi, Wang, Haijie, Zhang, Qixiao, Xie, Shuilin, Du, Hongli, Dai, Renke, Huang, Lizhen
Format: Article
Language:English
Subjects:
Antioxidants
Biomedical and Life Sciences
Biomedicine
Cell culture
Cell lines
Chemicals
CRISPR
Environmental Health
Hazard identification
Heme
Immunotoxicology
Occupational Medicine/Industrial Medicine
Organic chemistry
Oxygenase
Pharmacology/Toxicology
Plasmids
Skin
Skin tests
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/s00204-018-2287-8