Enzymatic conversion of 5-fluoro-2'-deoxyuridine to 5-fluorouracil or 5-fluoro-2'-deoxyuridine 5'-monophosphate in human tissues. 1990

M Uchida, and N Brown, and D H Ho
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

The relative activities and Km values of pyrimidine nucleoside phosphorylase (PNPase) and thymidine (TdR) kinase were compared in postsurgical human tissues. TdR kinase, which activates 5-fluoro-2'-deoxyuridine (FUdR), was higher in normal liver than in other tissues examined. PNPase, which cleaves FUdR, was higher in normal spleen and liver and lowest in kidney. In normal lung tissue, almost all of the FUdR was cleaved at a high concentration since PNPase activity was much higher than TdR kinase activity. The affinity of TdR kinase as indicated by Km was greater in normal than in cancerous lung tissue. At a low concentration, FUdR is relatively well activated in the normal tissue; thus it may not be suitable for chemotherapy of lung cancer. When comparing normal versus cancerous colon tissues, no difference was seen in either TdR kinase affinities or TdR kinase and PNPase activities. However, the PNPase affinity for FUdR was significantly higher in normal than in cancerous colon tissue. When FUdR is maintained at low concentrations, it might have a selective cytotoxicity for colon cancer tissue since it is well cleaved in normal colon.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010430 Pentosyltransferases Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental

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