Effect of methionine deprivation on L5178Y murine leukemia cells in culture interference with the antineoplastic effect of methotrexate

L5178Y cells in culture have a requirement for l-methionine which cannot be satisfied by supplying the components necessary for de novo biosynthesis [1]. Methionine deprivation produced a rapid and progressive loss of cell viability (30°_o by 6 hr: 90°_o by 24 hr). Cells which remained viable after being deprived of methionine could be rescued by l-methionine supplementation. L5178Y cells in culture were also highly sensitive to the folate antagonist, methotrexate. Exposure to a concentration of 10^-6 M for 6 hr resulted in a 95-97°_o loss of viability. However, if cells were deprived of methionine for 6 hr before exposure to methotrexate, the methotrexate effect was reduced. The cell-killing effect of melhotrexate was blocked by longer intervals of methionine deprivation. If the deprived cells were resupplied with the amino acid, the effect of methotrexate was still reduced for at least 12 hr following the methionine resupplementation.