Mechanism of growth inhibition by methotrexate.
The effect of methotrexate on the growth of Chinese hamster cells was examined under a variety of conditions. The experiments suggest that the important biological effects of methotrexate are the result of direct inhibition of thymidylate synthetase and one or both of the folate-dependent enzymes involved in a purine biosynthesis. In addition, analysis of the distribution of intracellular folate derivatives following methotrexate treatment gives no indication of accumulation of dihydrofolate, and accumulation that would be expected if inhibition of dihydrofolate reductase were the principal site of methotrexate action.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured / Q000378:metabolism*; D006224:Cricetinae; D005260:Female; D008727:Methotrexate / Q000494:pharmacology*; D010053:Ovary; D013763:Tetrahydrofolates / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D013763:Tetrahydrofolates; D013940:Thymidylate Synthase; D008727:Methotrexate