Newer Melanogenesis Control and Melanoma Eradication

Further advances leading to more sophisticated and effective suppression of melanogenesis and melanoma growth based on clarification and utilization of common vital factors involved in both processes are reviewed. Induction of depigmentation has been achieved by both glycosylation and its processing inhibitors, which have been found to be critical for the maturation and transport of tyrosinase from ribosomes through GERL-coated vesicles into premelanosomes. Kojic acid, a copper chelating melanogenic inhibitor, can induce inhibition of isolated tyrosinase activity as well as melanization in living pigment cells in in vitro and in vivo systems. This depigmenting effect was found to be due to a concurrent decrease in both eu- and pheomelanin formation. Malignant melanoma principally has accentuated melanosome genesis, which has been utilized to accumulate selectively ¹⁰B into melanoma cells using ¹⁰B-dopa analogue. Subsequent thermal neutron irradiation induces ¹⁰B(n, α)⁷Li reaction which releases high LET particles within a range of 10–14 μm thus erradicating selectively melanoma at the cellular level. This new therapy has been applied to a human melanoma lesion for the first time, and a successful therapeutic effect on melanoma has been obtained.     

Characterization of Melanogenesis in Normal Human Epidermal Melanocytes by Chemical and Ultrastructural Analysis

Chemical and ultrastructural studies were conducted to define the relationship between type of melanogenesis and fine structures of melanosomes in normal human epidermal melanocytes. Chemical analysis of epidermal melanin demonstrated that the ratio of eumelanin/pheomelanin varied individually, ranging from 1.31 to exclusively eumelanic. Ultrastructural analysis of fine structures of melanosomes revealed that spheroid melanosomes were frequently observed in melanocytes of the epidermis whose eumelanin/pheomelanin ratio was less than 5. Conversely, ellipsoid melanosomes predominated in melanocytes of the epidermis whose ratio was more than 10. On the basis of these findings, it seems reasonable to conclude that 1) normal human epidermal melanocytes synthesize both eumelanin and pheomelanin and 2) pheomelanin synthesis may be characterized by the presence of spheroid melanosomes whereas eumelanin synthesis is ascribed to ellipsoid melanosomes.     

DHICA Oxidase Activity of TRP1 and Interactions With Other Melanogenic Enzymes

Tyrosinase-related protein 1 (TRP1) maps to the brown locus in mice. Although the specific function of TRP1 has been in dispute, mutations in its structural gene result in the formation of brown rather than black melanin. We have investigated the melanogenic function of TRP1 by using immune-affinity purification of the protein and also by using transfection of its gene into fibroblasts to study its characteristics. We show that TRP1 has the ability to oxidize DHICA, a melanogenic intermediate derived from DOPAchrome. In addition, TRP1 has the ability to interact with tyrosinase and significantly stabilize the latter's catalytic function.