Pigment Transformation and Induction in Hamster Malignant Amelanotic Melanocytes

Hamster malignant amelanotic melanocytes were incubated in vitro with RNA and DNA from DMBA-induced hamster benign Blue Nevi. Of 6 experiments, temporary pigment induction occurred in 4, and permanent pigment transformation once. In the transformed culture, following initial pigmentation of more than 90% of cells, most of the pigment transformants subsequently died, but a stable population containing 1% heavily pigmented cells survived. The pigmented survivors exhibited markedly decreased in vitro growth capacity, proliferating only ⅕ as rapidly as the amelanotic cells. Amelanotic survivors showed features of increased contact inhibition including parallel orientation, decreased maximum plate density, and increased adherence to the culture plate. The latter feature alone also occurred temporarily in 4 cultures showing only pigment induction. It appears that benign Blue Nevi of hamsters contain genetic and epigenetic determinants of pigmentation lacking in malignant amelanotic melanocytes of this species. In addition, other genetic determinants seem to be present which are capable of modifying in vitro growth and surface properties of the malignant cells in the direction of more “normal” behavior. Under the conditions of these experiments, transfer both of a characteristic differentiated function, pigmentation, and of more “normal” growth and surface behavior characteristics from a benign melanoma to a malignant melanoma cell line has been observed. These findings suggest need for further experimental investigations to determine whether the neoplastic character of malignant melanoma is necessarily irreversible