Loading…
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...
Saved in:
| Published in: | Archives of toxicology 2018-10, Vol.92 (10), p.3103-3115 |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73 |
| container_end_page | 3115 |
| container_issue | 10 |
| container_start_page | 3103 |
| container_title | Archives of toxicology |
| container_volume | 92 |
| creator | Zhong, Guorui Li, Haojian Bai, Jing Pang, Shihui He, Changsheng Du, Xinyi Wang, Haijie Zhang, Qixiao Xie, Shuilin Du, Hongli Dai, Renke Huang, Lizhen |
| description | 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. |
| doi_str_mv | 10.1007/s00204-018-2287-8 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2091819193</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2091819193</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73</originalsourceid><addsrcrecordid>eNp1kMFqGzEQhkVJaZy0D5BLEOTSy7Yzkm1pj8a0ScDFlwRKL0IraV2la-1Gkg2bp-8udhII5DSH-f5_ho-QC4RvCCC-JwAG0wJQFoxJUcgPZIJTzgoQXJ6QCfApFDMxx1NyltIDADJZ8k_klAPyITmbkD8Lu9fB-LCh-a-jXXTWm-z3Pve0rWn65wNNLiSf_ZPOvg206qnuuqYfI5qGdu8aevNr_RtpdF0bs4s09Sm77WfysdZNcl-O85zc__xxt7wpVuvr2-ViVRguWC7QonWcCaFRTIWESlhegp7VIK0U2lheOVYaO7facAms1IaVdi4F1FhVVvBz8vXQ28X2cedSVlufjGsaHVy7S4pBiRJLLPmAXr1BH9pdDMN3IzVygs8HCg-UiW1K0dWqi36rY68Q1CheHcSrQbwaxSs5ZC6Pzbtq6-xL4tn0ALADkIZV2Lj4evr91v9_lI2u</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2090918736</pqid></control><display><type>article</type><title>Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system</title><source>Springer Nature</source><creator>Zhong, Guorui ; Li, Haojian ; Bai, Jing ; Pang, Shihui ; He, Changsheng ; Du, Xinyi ; Wang, Haijie ; Zhang, Qixiao ; Xie, Shuilin ; Du, Hongli ; Dai, Renke ; Huang, Lizhen</creator><creatorcontrib>Zhong, Guorui ; Li, Haojian ; Bai, Jing ; Pang, Shihui ; He, Changsheng ; Du, Xinyi ; Wang, Haijie ; Zhang, Qixiao ; Xie, Shuilin ; Du, Hongli ; Dai, Renke ; Huang, Lizhen</creatorcontrib><description>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.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-018-2287-8</identifier><identifier>PMID: 30132045</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>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</subject><ispartof>Archives of toxicology, 2018-10, Vol.92 (10), p.3103-3115</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>Archives of Toxicology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73</citedby><cites>FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30132045$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhong, Guorui</creatorcontrib><creatorcontrib>Li, Haojian</creatorcontrib><creatorcontrib>Bai, Jing</creatorcontrib><creatorcontrib>Pang, Shihui</creatorcontrib><creatorcontrib>He, Changsheng</creatorcontrib><creatorcontrib>Du, Xinyi</creatorcontrib><creatorcontrib>Wang, Haijie</creatorcontrib><creatorcontrib>Zhang, Qixiao</creatorcontrib><creatorcontrib>Xie, Shuilin</creatorcontrib><creatorcontrib>Du, Hongli</creatorcontrib><creatorcontrib>Dai, Renke</creatorcontrib><creatorcontrib>Huang, Lizhen</creatorcontrib><title>Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>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.</description><subject>Antioxidants</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell culture</subject><subject>Cell lines</subject><subject>Chemicals</subject><subject>CRISPR</subject><subject>Environmental Health</subject><subject>Hazard identification</subject><subject>Heme</subject><subject>Immunotoxicology</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Organic chemistry</subject><subject>Oxygenase</subject><subject>Pharmacology/Toxicology</subject><subject>Plasmids</subject><subject>Skin</subject><subject>Skin tests</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kMFqGzEQhkVJaZy0D5BLEOTSy7Yzkm1pj8a0ScDFlwRKL0IraV2la-1Gkg2bp-8udhII5DSH-f5_ho-QC4RvCCC-JwAG0wJQFoxJUcgPZIJTzgoQXJ6QCfApFDMxx1NyltIDADJZ8k_klAPyITmbkD8Lu9fB-LCh-a-jXXTWm-z3Pve0rWn65wNNLiSf_ZPOvg206qnuuqYfI5qGdu8aevNr_RtpdF0bs4s09Sm77WfysdZNcl-O85zc__xxt7wpVuvr2-ViVRguWC7QonWcCaFRTIWESlhegp7VIK0U2lheOVYaO7facAms1IaVdi4F1FhVVvBz8vXQ28X2cedSVlufjGsaHVy7S4pBiRJLLPmAXr1BH9pdDMN3IzVygs8HCg-UiW1K0dWqi36rY68Q1CheHcSrQbwaxSs5ZC6Pzbtq6-xL4tn0ALADkIZV2Lj4evr91v9_lI2u</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Zhong, Guorui</creator><creator>Li, Haojian</creator><creator>Bai, Jing</creator><creator>Pang, Shihui</creator><creator>He, Changsheng</creator><creator>Du, Xinyi</creator><creator>Wang, Haijie</creator><creator>Zhang, Qixiao</creator><creator>Xie, Shuilin</creator><creator>Du, Hongli</creator><creator>Dai, Renke</creator><creator>Huang, Lizhen</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20181001</creationdate><title>Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system</title><author>Zhong, Guorui ; Li, Haojian ; Bai, Jing ; Pang, Shihui ; He, Changsheng ; Du, Xinyi ; Wang, Haijie ; Zhang, Qixiao ; Xie, Shuilin ; Du, Hongli ; Dai, Renke ; Huang, Lizhen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antioxidants</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell culture</topic><topic>Cell lines</topic><topic>Chemicals</topic><topic>CRISPR</topic><topic>Environmental Health</topic><topic>Hazard identification</topic><topic>Heme</topic><topic>Immunotoxicology</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Organic chemistry</topic><topic>Oxygenase</topic><topic>Pharmacology/Toxicology</topic><topic>Plasmids</topic><topic>Skin</topic><topic>Skin tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Guorui</creatorcontrib><creatorcontrib>Li, Haojian</creatorcontrib><creatorcontrib>Bai, Jing</creatorcontrib><creatorcontrib>Pang, Shihui</creatorcontrib><creatorcontrib>He, Changsheng</creatorcontrib><creatorcontrib>Du, Xinyi</creatorcontrib><creatorcontrib>Wang, Haijie</creatorcontrib><creatorcontrib>Zhang, Qixiao</creatorcontrib><creatorcontrib>Xie, Shuilin</creatorcontrib><creatorcontrib>Du, Hongli</creatorcontrib><creatorcontrib>Dai, Renke</creatorcontrib><creatorcontrib>Huang, Lizhen</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Research Library (Corporate)</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Guorui</au><au>Li, Haojian</au><au>Bai, Jing</au><au>Pang, Shihui</au><au>He, Changsheng</au><au>Du, Xinyi</au><au>Wang, Haijie</au><au>Zhang, Qixiao</au><au>Xie, Shuilin</au><au>Du, Hongli</au><au>Dai, Renke</au><au>Huang, Lizhen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system</atitle><jtitle>Archives of toxicology</jtitle><stitle>Arch Toxicol</stitle><addtitle>Arch Toxicol</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>92</volume><issue>10</issue><spage>3103</spage><epage>3115</epage><pages>3103-3115</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><abstract>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><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30132045</pmid><doi>10.1007/s00204-018-2287-8</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-5761 |
| ispartof | Archives of toxicology, 2018-10, Vol.92 (10), p.3103-3115 |
| issn | 0340-5761 1432-0738 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2091819193 |
| source | Springer Nature |
| 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 |
| title | Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T18%3A09%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Advancing%20the%20predictivity%20of%20skin%20sensitization%20by%20applying%20a%20novel%20HMOX1%20reporter%20system&rft.jtitle=Archives%20of%20toxicology&rft.au=Zhong,%20Guorui&rft.date=2018-10-01&rft.volume=92&rft.issue=10&rft.spage=3103&rft.epage=3115&rft.pages=3103-3115&rft.issn=0340-5761&rft.eissn=1432-0738&rft_id=info:doi/10.1007/s00204-018-2287-8&rft_dat=%3Cproquest_cross%3E2091819193%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c372t-1d1de3277a174780b7d390a5f08d87acd3be29cd6dac38029ac29d6870f1bbd73%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2090918736&rft_id=info:pmid/30132045&rfr_iscdi=true |