Molecular Pharmacology, Vol 5, 303-317, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

Studies Relating to the Mode of Action of Methotrexate

II. Studies on Sites of Action in L-Cells in Vitro

¹ Ontario Cancer Institute and Department of Medical Biophysics, Toronto 5, Ontario, Canada

The methotrexate-induced inhibition of thymidylate and of purine synthesis has been studied in L-cells in tissue culture under conditions which permitted the separation of the two types of inhibition. Data are presented which suggest that under the conditions employed methotrexate may have sites of action in addition to its inhibition of folate and dihydrofolate reductase. These findings are discussed in relation to the strengths and weaknesses of the noe-site-of-action hypothesis.

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ACKNOWLEDGMENTS We thank Drs. W. R. Bruce and J. E. Till for helpful discussions.