A QUINAZOLINE ANTI-FOLATE AS INHIBITOR OF FOLATE METABOLISM IN MOUSE L-CELLS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 30  (2) , 193-201
Abstract
The effects of quinazoline antifolate CB 3703 [N-(p-[[(2,4-diamino-5-methyl-6-quinazolinyl)methyl]amino]benzoyl]-L-glutamic acid] on folate metabolism in mouse L-cells [neoplastic fibroblasts] were examined by measuring the amount of 14C label in folate derivatives and its distribution in separated folylmono- and polyglutamates in the cells grown in the presence of radioactive folate and quinazoline. The total radioactivity of folyl derivatives in the quinazoline-treated cells did not exceed 15% of the radioactivity extracted from the control cells, in spite of the fact that quinazoline CB 3703 did not interfere with the uptake of folate into L-cells. Analysis of folylmono- and polyglutamate derivatives, either incubated or not incubated with .gamma.-glutamylcarboxypeptidase, by chromatography on Sephadex G-25, G-15 or DEAE-cellulose revealed that in the quinazoline-treated cells, practically all radioactivity was found in the position of unmetabolized folate. Quinazoline CB 3703 apparently impairs in L-cells folate reduction and conversion to its coenzymatic forms and their subsequent polyglutamation causing a decrease in retention of folate derivatives in the quinazoline CB 3703-treated cells.

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