Certain mono- and dlhydroxybenzene derivatives are selectively cytotoxic for melanocytes In vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxiclty/hair depigmentation in C57BI mice by injection of 0.032ndash;1.0percnt; p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihy-droxyphenylalanlne (DOPA) or 3,4-dlhydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective Isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57BI mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 mu;M bovine serum albumin (BSA) In vitro varies widely, with tBCQ Gt; MMEHQ = DOPACQ DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyroslnase-generated 1,2-quinones. This mechanism evidently differs from that involved In In vitro hydroxybenzene melanocytotoxlclty of melanoma cells, in which active oxygen Intermediates generated by hydroxybenzene autoxldatlon play a significant role. The most reliable prognosticator of In vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reactina with orotein -SH.
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