Transplantable melanomas in gerbils (Meriones unguiculatus). II: melanogenesis.

We characterized the melanogenic apparatus in a family of transplantable gerbil melanomas (melanotic and amelanotic) using a combination of biophysical, ultrastructural and biochemical methods. Melanotic melanomas produced pure eumelanin but in vesiculo-globular melanosomes ('pheomelanosomes'); the eumelanosomes, characteristically ellipsoidal in shape with fibrillar or fibrillo-lamelar matrix, were never noticed. Melanotic melanomas also had significant tyrosinase activity and Zn, Pb/S, Ca and P content; all higher than in the amelanotic variants. The amelanotic variant, which was devoid of melanin pigment and melanosomes, had clearly detectable tyrosinase activity (albeit at 20% of that in the melanotic variant). Thus, with these multidirectional approaches we demonstrate that pure eumelanin can be synthesized in organelles ultrastructurally defined as pheomelanosomes, but a defect in the formation of melanosomes can prevent in vivo melanin synthesis despite the presence of detectable tyrosinase activity. We conclude that this melanoma system provides an excellent experimental model for the study of molecular components determining pheo- and/or eumelanogenesis. The information generated can be used for defining the roles of melanogenesis and of tyrosinase expression in the regulation of melanoma behavior and the effect of their modification on the course of the disease.