PSORALENS STIMULATE MOUSE MELANOCYTE AND MELANOMA TYROSINASE ACTIVITY IN THE ABSENCE OF ULTRAVIOLET-LIGHT

Psoralens (8-methoxypsoralen, 5-methoxypsoralen and 4, 5, 8-trimethylpsoralen) stimulate mouse melanoma cell (S91 and B16/F10) tyrosinase activity in vitro in a dose-related manner. Stimulation of enzyme activity by the psoralens was evoked in the presence or absence of light. In the presence of a melanotropin the actions of the psoralens were generally at least additive compared to the individual actions of the two agonists. The actions of the psoralens were acute and depended upon the constant presence of the agents to maintain enhanced melanoma tyrosinase activity. Tyrosinase activation by the psoralens, like that of alpha-melanotropin, was blocked by actinomycin-D or cycloheximide demonstrating that the actions of the drugs may have involved both transcriptional and translational events in the stimulation of melanogenesis. Psoralens also stimulated an immediate darkening of frog skins in vitro. Topically applied psoralens were transdermally delivered to the systemic circulation resulting in a conversion from pheomelanogenesis to eumelanogenesis within follicular melanocytes throughout the entire skin of mice (C57BL/6JA(y) maintained in the dark. Taken together, these results demonstrate that psoralens activate processes within melanocytes resulting in both an immediate translocation of melanosomes within the cell (frog) or in a slower genomic event involving tyrosinase activation (melanoma cells) and eumelanin formation (mouse follicular melanocytes).