{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:50:42Z","timestamp":1787068242533,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T00:00:00Z","timestamp":1445990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Although photoallergens require UV energy for antigen formation, the subsequent immune response is considered to be the same as in ordinary skin sensitization. Therefore,\n                    <jats:italic>in vitro<\/jats:italic>\n                    tests for skin sensitization should also be applicable for photoallergy testing. In this study, we examined whether activation of the Keap1 (Kelch\u2010like ECH\u2010associated protein 1)\u2013Nrf2 (nuclear factor\u2010erythroid 2\u2010related factor 2)\u2013ARE (antioxidant response element) pathway could be used to assess the photoallergenic potential of chemicals, using the reporter cell line AREc32 or KeratinoSens\n                    <jats:sup>TM<\/jats:sup>\n                    . First, we identified an appropriate UVA irradiation dose [5 J cm\n                    <jats:sup>\u20132<\/jats:sup>\n                    irradiation in phosphate\u2010buffered saline (PBS)] by investigating the effect of UV irradiation on ARE\u2010dependent gene induction using untreated or 6\u2010methylcoumarin (6\u2010MC)\u2010treated cells. Irradiation of well\u2010known photoallergens under this condition increased ARE\u2010dependent gene expression by more than 50% compared with both vehicle and non\u2010irradiated controls. When the cut\u2010off value for detecting photoallergens was set at 50% induction, the accuracy of predicting photoallergenic\/phototoxic chemicals was 70% in AREc32 cells and 67% in KeratinoSens\n                    <jats:sup>TM<\/jats:sup>\n                    cells, and the specificity was 100% in each case. We designate these assays as a photo\u2010ARE assay and photo\u2010KeratinoSens\n                    <jats:sup>TM<\/jats:sup>\n                    , respectively. Our results suggest that activation of the Keap1\u2010Nrf2\u2010ARE pathway is an effective biomarker for evaluating both photoallergenic and phototoxic potentials. Either of the above tests might be a useful component of a battery of\n                    <jats:italic>in vitro<\/jats:italic>\n                    tests\/\n                    <jats:italic>in silico<\/jats:italic>\n                    methods for predicting the photoallergenicity and phototoxicity of chemicals. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/jat.3234","type":"journal-article","created":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T00:37:02Z","timestamp":1446079022000},"page":"956-968","source":"Crossref","is-referenced-by-count":14,"title":["Development of novel\n                    <i>in vitro<\/i>\n                    photosafety assays focused on the Keap1\u2013Nrf2\u2013ARE pathway"],"prefix":"10.1002","volume":"36","author":[{"given":"Kyoko","family":"Tsujita\u2010Inoue","sequence":"first","affiliation":[{"name":"Shiseido Research Center Shiseido Co. Ltd  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morihiko","family":"Hirota","sequence":"additional","affiliation":[{"name":"Shiseido Research Center Shiseido Co. Ltd  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Atobe","sequence":"additional","affiliation":[{"name":"Shiseido Research Center Shiseido Co. Ltd  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Ashikaga","sequence":"additional","affiliation":[{"name":"Shiseido Research Center Shiseido Co. Ltd  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Tokura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hamamatsu University School of Medicine  1\u201020\u20101 Handayama, Higashi\u2010ku Hamamatsu Shizuoka 431\u20103192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kouzuki","sequence":"additional","affiliation":[{"name":"Shiseido Research Center Shiseido Co. 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