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The growth and DNA synthesis of L1210 mouse leukemia cells were examined under folate- and methionine-deficient conditions. Cell proliferation was dependent on methionine supplementation rather than on folate concentration. The UdR suppression value was abnormally high in the folate-deficient condition. However, it was also high when the methionine was low, despite folate supplementation. In accordance with this, UdR incorporation was significantly improved with various folates by cells grown in low-methionine conditions. Methionine depletion resulted in marked impairment of UdR incorporation regardless of folate concentration. These findings indicate close metabolic interrelations between folate and methionine, which may be relevant to the pathological biochemistry of human megaloblastic anemia.

Growth and DNA synthesis of folate-and methionine-depleted L1210 mouse leukemia cells in culture.