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However, there have been several reports of its adverse reactions, namely photosensitivity with intense inflammatory rashes and subsequent skin cancer development. To assess the effects of photosensitizing drugs voriconazole and hydrochlorothiazide (<jats:styled-content style=\"fixed-case\">HCTZ<\/jats:styled-content>) on the enhancement of <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>\u2010induced inflammatory responses and <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>\u2010induced tumorigenesis, we utilized <jats:italic>Xpa<\/jats:italic>\u2010knockout mice, which is <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair\u2010deficient and more susceptible to <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>\u2010induced inflammation and tumor development than wild\u2010type mice. Administration of voriconazole prior to broadband <jats:styled-content style=\"fixed-case\">UVB<\/jats:styled-content> exposure significantly upregulated multiple inflammatory cytokines compared with the vehicle\u2010 or <jats:styled-content style=\"fixed-case\">HCTZ<\/jats:styled-content>\u2010administered groups. Voriconazole administration along with chronic <jats:styled-content style=\"fixed-case\">UVB<\/jats:styled-content> exposure produced significantly higher number of skin tumors than <jats:styled-content style=\"fixed-case\">HCTZ<\/jats:styled-content> or vehicle in <jats:italic>Xpa<\/jats:italic>\u2010knockout mice. Furthermore, the investigation of <jats:styled-content style=\"fixed-case\">UVB<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage using embryonic fibroblasts of <jats:italic>Xpa<\/jats:italic>\u2010knockout mice revealed a significantly higher 8\u2010oxo\u20107,8\u2010dihydroguanine level in cells treated with voriconazole N\u2010oxide, a voriconazole\u2010metabolite during <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> exposure. The data suggest that voriconazole plus <jats:styled-content style=\"fixed-case\">UVB<\/jats:styled-content>\u2010induced inflammatory response may be related to voriconazole\u2010induced skin phototumorigenesis.<\/jats:p>","DOI":"10.1111\/php.12972","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T13:56:02Z","timestamp":1530626162000},"page":"1077-1081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inflammation Due to Voriconazole\u2010induced Photosensitivity Enhanced Skin Phototumorigenesis in <i>Xpa<\/i>\u2010knockout Mice"],"prefix":"10.1111","volume":"94","author":[{"given":"Makoto","family":"Kunisada","sequence":"first","affiliation":[{"name":"Division of Dermatology Department of Internal Related Kobe University Graduate School of Medicine Kobe 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