Cloning and expression of cDNA for human dihydropyrimidine dehyd

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435 912, 536 243, 536 2431, 536 2432, 536 2433, C12Q 168, C12P 1534, C07H 2104

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active

060156732

ABSTRACT:
The invention relates to methods and compositions that are useful for detecting deficiencies in dihydropyrimidine dehydrogenase (DPD) levels in mammals including humans. Cancer patients having a DPD deficiency are at risk of a severe toxic reaction to the commonly used anticancer agent 5-fluorouracil (5-FU). Claimed are DPD genes from human and pig, methods for detecting the level of nucleic acids that encode DPD in a patient, and nucleic acids that are useful as probes for this purpose. Also claimed are methods for expressing DPD in heterologous organisms. Expression vectors that employ a DPD nucleic acid as a selectable marker are also claimed. This selectable marker functions in both prokaryotes and eukaryotes.

REFERENCES:
Cheng et al, "Molecular cloning of dihydropyrimidine dehydrogenase", Clin. Pharm. Therap. 55(2):188, Feb. 1994.
Gaedgk et al, "Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse drug reactions", Pharmacogenetics 4(3):142-153 Abstract Only, Jun. 1994.
Lu et al, "Dihydropyrimidine dehydrogenase activity in human peripheral blood mononucleasr cells and liver: Population characteristics, newly identified patients and clinical implication in 5-fluorouracil therapy", Cancer Research 53:5433-5438, Nov. 1993.

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