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Science 14 September 1979:
Vol. 205. no. 4411, pp. 1135 - 1137
DOI: 10.1126/science.472732
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Articles
Science, Vol 205, Issue 4411, 1135-1137
Copyright © 1979 by American Association for the Advancement of Science
Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism
E Cadman,
R Heimer,
and
L Davis
Exposure of L1210 leukemia cells first to 0.1 to 100 micromolar methotrexate and then to 10 micromolar 5-fluorouracil produces a synergistic effect on the number of cells killed in culture. Methotrexate dose-related increases occur in the concentrations of intracellular 5-fluorouracil ribonucleotides and 5-fluoro-2'-deoxyuridylate and in the incorporation of 5-fluorouracil into RNA. These increases are correlated with increased concentrations of intracellular phosphoribosylpyrophosphate. It is proposed that the enhanced formation of ribonucleotides of 5-fluorouracil and the subsequent incorporation of these compounds into RNA in methotrexate-treated cells may account for synergism between these agents.
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