Reversion to methionine independence in simian virus 40-transformed human and malignant rat fibroblasts is associated with altered ploidy and altered properties of transformation

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Abstract
Many transformed and malignant cells, unlike normal cells, do not grow when methionine in the growth medium is replaced by its immediate precursor homocysteine. Rare cells from those populations revert to methionine independence. Methionine-independent revertants of both human fibroblasts transformed by SV-40 and malignant rat fibroblasts concomitantly revert for some of the properties associated with the transformed state. Of the 13 methionine-independent revertants described here, 5 showed increased anchorage dependence as reflected by reduced cloning efficiencies in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and, 3 altered their cell morphology significantly. Of the 13, 8 have increased chromosome numbers. All lines tested contained immunologically identifiable tumor antigen of SV-40. By selecting for methionine independence it is possible to select for heterogeneous transformation revertants, indicating further a relationship between altered methionine metabolism and oncogenic transformation. A positive metabolic method to select for transformation revertants was developed, and its use resulted in selection of human transformation revertants.