Abstract:
:Exposure of tumor cells to reduced folates before or with the fluoropyrimidines, 5-fluorouracil or 5-fluoro-2'deoxyuridine, results in a substantial increase in the activity of these drugs. Available evidence suggests that the mechanism of this synergism is a kinetic stabilization of complex formed between thymidylate synthase and fluorodeoxyuridylate that also involves a mole of the cofactor for the thymidylate synthase reaction, 5,10-methylenetetrahydrofolate. This effect results in an extended time of depletion of thymidine nucleotides with a resultant increased level of cell death. The biochemical aspects of this interaction are discussed and related to the therapeutics of this combination.
journal_name
Cancerjournal_title
Cancerauthors
Morgan RGdoi
10.1002/1097-0142(19890315)63:6+<1008::aid-cncr282subject
Has Abstractpub_date
1989-03-15 00:00:00pages
1008-12issue
6 Suppleissn
0008-543Xissn
1097-0142journal_volume
63pub_type
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