title: Selective cytotoxicity of hydroquinone for melanocyte-derived cells is mediated by tyrosinase activity but independent of melanin content.
abstract: In previous studies we have shown melanotic melanomas to be exquisitely more sensitive to hydroquinone (HQ) inhibition than non-melanotic cell lines in vitro. Indeed, incorporation of [H3] Urd and [H3] Thd have been shown to be respectively 80 and 35 times more sensitive to HQ inhibition. The difference between the cell lines studied was their derivation, marked by their different melanin contents. The presence of melanin was proposed as a possible explanation of the differences. However, comparative experiments reported here demonstrate that amelanotic melanoma cell lines are equally susceptible to HQ inhibition. Thus, the action of HQ is apparently independent of the melanin content of the cell. Significantly, the tyrosinase levels in the melanomas and the amelanomas were found to be comparable and markedly different from that in the non-melanoma control cell lines. Thus, the results reported here support the hypothesis put forward by other workers that hydroquinone melanotoxicity is independent of cellular melanin content but requires the presence of active tyrosinase.
authors.affiliation: Research Division, North East Wales Institute, Deeside, Clwyd, United Kingdom.
authors.forename: C J
authors.initials: CJ
authors.lastname: Smith
authors.forename: K B
authors.initials: KB
authors.lastname: O'Hare
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
mesh_terms: D000818:Animals; D004156:Catechol Oxidase / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D008543:Melanins / Q000502:physiology*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D002583:Uterine Cervical Neoplasms
chemical_list: D004273:DNA, Neoplasm; D006873:Hydroquinones; D008543:Melanins; D012334:RNA, Neoplasm; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase