Effect of nutritional and enzymatic methionine deprivation upon human normal and malignant cells in tissue culture.

Human embryonic lung fibroblasts (F-136-35-56) capable of growing in medium containing DL-homocysteine instead of L-methionine and human acute lymphoblastic leukemia cells (CCRF-HSB-2) with absolute methionine requirement exhibited dose-dependent growth inhibition when semipurified L-methionine-degrading enzyme (L-methioninase, EC 4.4.1.11) was added to the tissue cultures. When D-homocystine was added to the cultures together with L-methioninase (0.1 units/ml, which completely degraded the available L-methionine in tissue culture), the F-136-35-56 cells continued to grow whereas the CCRF-HSB-2 cells were completely inhibited. In mixed cultures of the two cell lines with added L-methioninase + D-homocystine or L-methioninase + L-homocysteine thiolactone, the normal fibroblasts grew and synthesized DNA vigorously, whereas the lymphocytic malignant cells lost their viability completely and died within 3 to 4 days.