Role of folylpolyglutamates in biochemical modulation of fluoropyrimidines by leucovorin.

Journal Article

The growth-inhibitory effect of fluoropyrimidines combined with a short-term exposure to leucovorin and the pattern of polyglutamylation of folates were compared between parental CCRF-CEM cells and a cell line with impaired ability to form polyglutamates (CCRF-CEM/P). The combination of leucovorin with 5-fluorouracil or 5-fluorodeoxyuridine increased the growth inhibition of CCRF-CEM cells compared to the fluoropyrimidine alone in the parent cell line but not in CCRF-CEM/P cells. In addition, leucovorin produced a significant increase in the inhibition of intracellular thymidylate synthase activity caused by 5-fluorouracil or 5-fluorodeoxyuridine as compared to these drugs alone in CCRF-CEM cells, but no increase in inhibition over that produced by the single drugs alone was observed in CCRF-CEM/P cells. Although levels of 5,10-methylene tetrahydrofolate after leucovorin administration were similar in both cell lines, polyglutamylation of this coenzyme was decreased in the CCRF-CEM/P cell line. The inability of CCRF-CEM/P cells to form significant levels of polyglutamates of N5,N10-methylenete-trahydrofolate, may be responsible for the lack of enhanced cell kill observed when a short exposure to leucovorin is used with fluoropyrimidines.

Full Text

Duke Authors

Cited Authors

  • Romanini, A; Lin, JT; Niedzwiecki, D; Bunni, M; Priest, DG; Bertino, JR

Published Date

  • February 1, 1991

Published In

Volume / Issue

  • 51 / 3

Start / End Page

  • 789 - 793

PubMed ID

  • 1988119

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng

Conference Location

  • United States