Abstract
Transport of Methotrexate and other folate compounds into cells of L1210 mouse leukemia or Lactobacillus casei occurs via “active,” carrier-mediated processes. In the bacterial system, transport is linked to glycolysis and is unaffected by cyclic nucleotides. A folate-binding protein, believed to be the carrier in the transport process, has been solubilized by treatment of L. casei membranes with Triton X-100 in the presence of [ 3H]folate and purified to homogeneity. The protein (MW 25,000) binds an equimolar amount of folate. Owing to a preponderance of hydrophobic amino acids, the binding protein is insoluble in aqueous media unless encased in a Triton micelle. Similar experiments suggest that L1210 cells may contain a Triton-extractable membrane protein that binds 5-methyl tetrahydrofolate and Methotrexate. Transport of Methotrexate into L1210 cells is depressed by exogenous cyclic nucleotides or compounds that elevate the level of endogenous cyclic nucleotides, such as phosphodiesterase inhibitors, adenyl cyclase stimulators, glucose, ATP, ADP and GTP. Implications of these observations for cancer chemotherapy are discussed.
Published Version
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