| Abstract: |
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 inhi bition of intracellular thymidylate synthase activity caused by 5-fluorour acil or 5-fluorodeoxyuridine as compared to these drugs alone in CCRFCEM 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 de creased in the CCRF-CEM/P cell line. The inability of CCRF-CEM/P cells to form significant levels of polyglutamates of N5,N10-methylenetetrahydrofolate, may be responsible for the lack of enhanced cell kill observed when a short exposure to leucovorin is used with fluoropyrimi dines. © 1991, American Association for Cancer Research. All rights reserved. |
| Keywords: |
controlled study; human cell; fluorouracil; methotrexate; t-lymphocytes; cell division; cell line; drug resistance; dose-response relationship, drug; tumor cells, cultured; drug synergism; cell culture; folinic acid; thymidylate synthase; floxuridine; leucovorin; growth inhibition; lymphoblast; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; pteroylpolyglutamic acids; pteroptin
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