Ultrastructural and biochemical observations on the effect of 4-hydroxyanisole plus tyrosinase on normal human melanocytes and keratocytes in tissue culture.
Cultures of melanocytes and keratocytes were exposed to 15 micrograms ml-1 tyrosinase and 4-hydroxyanisole (4-OHA) 5 X 10(-4) M to 5 X 10(-2) M for 1 to 24 h. No damage was suffered by either cell below 5 X 10(-3) M 4-OHA for 6 h, but higher concentrations and longer exposures extensively damaged both cells. Exposure of cells washed free of culture medium to tyrosinase and 4-OHA 1 X 10(-3) M for 1 h resulted also in extensive damage. This indicates that an early-formed toxic product of the reaction between tyrosinase and 4-OHA is inactivated by constituents of the medium. This was confirmed by Liquid Chromatography and Scanning Spectrophotometry which showed that a toxic 4-OHA quinone immediately reacted with nucleophilic substances in the medium resulting in products which, on accumulation, are probably responsible for the later (6 h plus) damage to melanocytes and keratocytes. A possible effect of allegedly specific melanocytotoxic drugs on keratocytes should always be borne in mind with tissue culture experiments.
D000840:Anisoles / Q000494:pharmacology*; D004156:Catechol Oxidase / Q000494:pharmacology*; D003470:Culture Media; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000494:pharmacology*
D000840:Anisoles; D003470:Culture Media; C009760:mequinol; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase