BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in catabolism of pyrimidines including 5-fluorouracil. There have been efforts to isolate a monoclonal antibody that will bind selectively to pyrimidine and can be used to measure the concentration of pyrimidine in blood and/or in urine that may reflect the activity of dihydropyrimidine dehydrogenase. However, the monoclonal antibodies selective to pyrimidine have not been available. METHODS: Using 1-carboxymethyl-uracil as a hapten, in which steric conformation of uracil is thought to be well maintained, extensive screening was done to isolate a monoclonal antibody specific to uracil. RESULTS: We established the first monoclonal antibody that reacted with uracil and thymine but not with pseudouridine, dihydrouracil, dihydrothymine, cytosine, uridine, or N-carbamyl-beta-alanine at the concentration of 100 microg/ml. CONCLUSIONS: The monoclonal antibody can be used to develop a simple screening assay for patients with dihydropyrimidine dehydrogenase deficiency. This may increase the safety of 5-fluorouracil treatment. Copyright 2002 Elsevier Science B.V.
BACKGROUND:Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in catabolism of pyrimidines including 5-fluorouracil. There have been efforts to isolate a monoclonal antibody that will bind selectively to pyrimidine and can be used to measure the concentration of pyrimidine in blood and/or in urine that may reflect the activity of dihydropyrimidine dehydrogenase. However, the monoclonal antibodies selective to pyrimidine have not been available. METHODS: Using 1-carboxymethyl-uracil as a hapten, in which steric conformation of uracil is thought to be well maintained, extensive screening was done to isolate a monoclonal antibody specific to uracil. RESULTS: We established the first monoclonal antibody that reacted with uracil and thymine but not with pseudouridine, dihydrouracil, dihydrothymine, cytosine, uridine, or N-carbamyl-beta-alanine at the concentration of 100 microg/ml. CONCLUSIONS: The monoclonal antibody can be used to develop a simple screening assay for patients with dihydropyrimidine dehydrogenase deficiency. This may increase the safety of 5-fluorouracil treatment. Copyright 2002 Elsevier Science B.V.
Authors: Daniel Kozo; Matt W Ross; Justin Jarrah; Michael Barrett; Rebecca L Harney; Jodi B Courtney; Irina Baburina; Julianne L Holleran; Jan H Beumer; Godefridus J Peters; Richard J Honeywell; Salvatore J Salamone Journal: Ther Drug Monit Date: 2017-06 Impact factor: 3.681