By exposing an established cell line of malignant mouse lymphocytic cells (L5178Y) to a culture environment low in calcium and magnesium, we have isolated and maintained in continuous culture a variant population with reduced growth requirements for the cations. The variant cells are larger, have enhanced aggregability, tend to form dispersed colonies in semisolid medium, and have increased oncogenicity. Variants and their progenitors share similar morphology, maximum proliferative rate, and stability of phenotype. The significance of these findings is discussed and an analogy suggested between the selective influence of calcium and magnesium deprivation in vitro and the evolution of thymic dysplasias in divalent cation- deprived rodents.

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