Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.
The aim of this study was to find differentially regulated genes in THP-1 monocytic cells exposed to sensitizers and nonsensitizers and to investigate if such genes could be reliable markers for an in vitro predictive method for the identification of skin sensitizing chemicals. Changes in expression of 35 genes in the THP-1 cell line following treatment with chemicals of different sensitizing potential (from nonsensitizers to extreme sensitizers) were assessed using real-time PCR. Verification of 13 candidate genes by testing a large number of chemicals (an additional 22 sensitizers and 8 nonsensitizers) revealed that prediction of contact sensitization potential was possible based on evaluation of changes in three genes: IL8, HMOX1 and PAIMP1. In total, changes in expression of these genes allowed correct detection of sensitization potential of 21 out of 27 (78%) test sensitizers. The gene expression levels inside potency groups varied and did not allow estimation of sensitization potency of test chemicals. Results of this study indicate that evaluation of changes in expression of proposed biomarkers in THP-1 cells could be a valuable model for preliminary screening of chemicals to discriminate an appreciable majority of sensitizers from nonsensitizers.
Arkusz
Joanna
J
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348 Łódź, Poland. joanna@imp.lodz.pl
Stępnik
Maciej
M
Sobala
Wojciech
W
Dastych
Jarosław
J
D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000826:Animal Testing Alternatives; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005562:Formazans / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000378:metabolism; D015262:Xenobiotics / Q000145:classification / Q000633:toxicity*
D000485:Allergens; D015415:Biomarkers; C508606:CXCL8 protein, human; D005562:Formazans; D016209:Interleukin-8; D010455:Peptides; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D015262:Xenobiotics; C054616:Paim I; C079782:MTT formazan; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1