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To explore the mechanism underlying that effect, we previously showed that oxidation of RD with mushroom tyrosinase produces RD\u2010quinone, which is converted to secondary quinone products, and we suggested that those quinones are cytotoxic because they bind to cellular proteins and produce reactive oxygen species. We then confirmed that human tyrosinase can oxidize both enantiomers of RD. In this study, we examined the metabolism of RD in B16F1 melanoma cells in\u00a0vitro. Using 4\u2010amino\u20103\u2010hydroxy\u2010<jats:italic>n<\/jats:italic>\u2010butylbenzene as a specific indicator, we detected moderate levels of RD\u2010pheomelanin in B16F1 cells exposed to 0.3 to 0.5\u00a0mM RD for 72\u00a0h. We also confirmed the covalent binding of RD\u2010quinone to non\u2010protein thiols and proteins through cysteinyl residues. The covalent binding of RD\u2010quinone to proteins was 20\u2010 to 30\u2010fold greater than dopaquinone. These results suggest that the tyrosinase\u2010induced metabolism of RD causes melanocyte toxicity.<\/jats:p>","DOI":"10.1111\/pcmr.12363","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T13:58:55Z","timestamp":1424872735000},"page":"295-306","source":"Crossref","is-referenced-by-count":39,"title":["Tyrosinase\u2010catalyzed metabolism of rhododendrol (RD) in B16 melanoma cells: production of RD\u2010pheomelanin and covalent binding with thiol proteins"],"prefix":"10.1111","volume":"28","author":[{"given":"Shosuke","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masae","family":"Okura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Ojika","sequence":"additional","affiliation":[{"name":"Department of Applied Molecular Biosciences Graduate School of Bioagricultural Sciences Nagoya University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiharu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9902082"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.16"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26226"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.050"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx6003584"},{"key":"e_1_2_6_7_1","first-page":"2543","article-title":"Selective toxicity of 5\u2010S\u2010cysteinyldopa, a melanin precursor, to tumor cells in\u00a0vitro and in\u00a0vivo","volume":"40","author":"Fujita K.","year":"1980","journal-title":"Cancer Res."},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/S0026-895X(25)13536-0","article-title":"Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6\u2010hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in\u00a0vitro","volume":"14","author":"Graham D.G.","year":"1978","journal-title":"Mol. 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