ULTRASTRUCTURAL OBSERVATIONS ON THE EFFECT OF 4-HYDROXYANISOLE ON NORMAL HUMAN MELANOCYTES IN TISSUE-CULTURE

[摘要] There is considerable current interest in the possible therapeutic application of melanocytotoxic chemicals to the treatment of melanoma, and tissue culture of melanocytes provides an obvious tool for investigating and monitoring their effects. Riley''s classic 1970 experiment showing a specific cytotoxic effect of 4-hydroxyanisole (4-OHA) on tissue-cultured melanocytes of black guinea pig ear skin was repeated on normal human melanocytes and the results were examined by EM. In dispersed tissue culture, no specific toxic effect on human melanocytes was observed after equally timed exposures to similar (10-3 M) or even higher (10-2 M) concentrations of the drug; plasma membrane, nucleus and cytoplasmic organelles, including melanosomes were unaffected. The same applied to melanocytes of whole epidermis exposed for 5 h to the same concentrations of 4-OHA in culture medium. Melanocytes of PUVA [8-methoxypsoralen longwave UV light] treated skin similarly exposed for up to 24 h to 10-2 and 10-3 M 4-OHA, did not exhibit morphological damage at the ultrastructural level. The discrepancy of results between guinea pig and man could possibly be explained by a relatively low level of active tyrosinase in the human melanocytes (Riley believes the cytotoxic effect of 4-OHA to be due to the fact that it acts as a substrate for tyrosinase, toxic intermediates being liberated as a result). The lack of effect on the PUVA-activated melanocytes indicates that this cannot be the entire explanation.