Regulation of malanin synthesis in mammalian cells: effect of gene dosage on the expression of differentiation.

Near-tetraploid (2S), pigmented, Syrian hamster cells (3460(2)) were hybridized with unpigmented mouse fibroblasts to produce hybrids that contained two pigment cell genomes and one fibroblast genome per cell (3(2)D). Half of the hybrids were pigmented and showed high activity of the enzyme dihydroxyphenylalanine oxidase; the other half of the hybrids were unpigmented and devoid of the activity of this enzyme. (In contrast, all the previously isolated hybrids containing only one pigment cell genome and one fibroblast genome were unpigmented.) Analyses of the chromosome complement and of a series of enzymes unrelated to melanin synthesis did not reveal any great differences between the pigmented and unpigmented 3(2)D hybrids. Upon the isolation of subclones, unpigmented 3(2)D hybrids produced only unpigmented colonies, whereas pigmented hybrids produced both pigmented and unpigmented colonies. Although the mechanism that results in the formation of some pigmented and some unpigmented hybrids in these experiments is not known, it is clear that the number of pigment cell genomes in a hybrid affects the expression of pigmentation.