RT Journal Article SR Electronic T1 Mechanisms of excision of 5-fluorouracil by uracil DNA glycosylase in normal human cells. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 854 OP 857 VO 43 IS 6 A1 D J Mauro A1 J K De Riel A1 R J Tallarida A1 M A Sirover YR 1993 UL http://molpharm.aspetjournals.org/content/43/6/854.abstract AB Recent evidence indicates that 5-fluorouracil (5-FlUra) is incorporated into DNA and is removed by the DNA repair enzyme uracil DNA glycosylase. Synthetic oligonucleotides containing either a single uracil or 5-FlUra residue were constructed to examine the mechanisms by which human cells remove 5-FlUra from DNA. The human uracil DNA glycosylase excised uracil in a manner similar to that observed for the bacterial enzyme. In contrast, a significant difference was observed in their abilities to remove 5-FlUra. In particular, both the bacterial and normal human enzymes displayed 13-17-fold increases in their apparent Km values but the apparent Vmax values remained virtually constant. These results demonstrate that normal human cells possess a defined capacity to remove 5-FlUra incorporated into DNA. However, specific kinetic differences may exist that affect their capacity to remove 5-FlUra formed in DNA after treatment with this cancer chemotherapeutic agent.