Thymidine Phosphorylase Activity in Plasma: A Cancer Marker or an Artifact of Ultrafiltration?

Woodman, Peter W.

doi:10.3181/00379727-162-40640

Cited by 3 publications

(3 citation statements)

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“…A previous report (Palu, 1980) has suggested that TP activity may be a marker of cell maturation in leukemic cells, consistent with our finding of higher TP activity in the MNB-T2 cells. Conversely, another report (Pauly et al, 1978) has suggested that the activity of this enzyme in plasma could be used as a cancer marker, but the findings in that report were later disputed because of a possible artifact (Woodman, 1979). The high ratios of TP to DPD specific activity in both cell lines indicated that DPD is the rate-limiting enzyme of pyrimidine degradation in MNB.…”

Section: Discussionmentioning

confidence: 97%

Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells

Williams

Tuchman

1989

Intl Journal of Cancer

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The C-1300 neuroblastoma tumor which arises spontaneously in the A/J mouse has been maintained in this mouse strain. Two different cell populations have been recognized in cultured C-1300 mouse neuroblastoma (MNB): (1) round, "neuroblast-like" cells, growing in suspension (poorly attached), that have a highly malignant behavior when injected into the A/J mouse (T1 cells); and (2) flat, "epithelioid" cells that attach well to surfaces and show low malignancy towards the inoculated animals (T2 cells). The specific activities of the pyrimidine metabolizing enzymes thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) were examined in both MNB cell lines by a new radiochromatographic method. Enzymatic activities of TP and DPD in the cytosols of T2 (weakly malignant) cells were up to 15 times higher than those of T1 (strongly malignant) cells, whereas the mean TP/DPD activity ratio was 16 in either cell line. TP and DPD activity levels increased with time of growth in culture in T2 cells while no such increase was seen in the T1 cells. Maximal TK activity was similar in both cell lines but dropped more rapidly in the T2 cells as cell densities increased. The enzymatic activity levels of TP and DPD but not of TK correlated inversely with neoplastic expression of MNB cells. The observed patterns of pyrimidine metabolizing enzymes in MNB cells could result in an increased thymidine pool in T1 cells whenever TK activity is suppressed, whereas such conditions would favor the generation of thymine in the T2 cells.

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Section: Discussionmentioning

confidence: 97%

Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells

Williams

Tuchman

1989

Intl Journal of Cancer

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“…One site of extrahepatic metabolism, as found in our pre-liminary studies, is the bloodstream. Woodman et al ( 18,33) have shown that circulating granulocytes contain thymidine phosphorylase, a nucleoside phosphorylase that can catalyze the conversion of FdUrd to FUra. Hepatic metabolism is nevertheless an important site of FdUrd removal as shown by several findings, including the poor oral bioavailability and effectiveness (3 1) of the drug, and the hepatic extraction ratio of 0.7 to 0.9 demonstrated during continuous iv infusion ( 15).…”

Section: Time Rninmentioning

confidence: 98%

“…Arterial blood samples were collected in heparinized tubes, which were immediately placed in ice and centrifuged at 5 "C within 15 rnin to minimize the metabolism of FdUrd to FUra by granulocytes ( 18) after removal from the body. Preliminary experiments, in which the metabolism of FdUrd to FUra by whole blood in vitro was assessed using a high-performance liquid chromatographic method for fluoropyrimidine analysis, showed conversions of 2% of the total FdUrd (initial concentration 203 p M ) in 30 rnin at 5°C and 17% in 30 rnin at 37°C.…”

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confidence: 99%

Dose-Dependent Elimination of 5-Fluoro-2'-deoxyuridine in the Monkey

Williams

Huang

Chen

et al. 1987

Experimental Biology and Medicine

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The kinetics of 5-fluoro-2'deoxyuridine (FdUrd) and 5-flUOrO~d (FUra) disposition after bolus intravenous injection were determined in anesthetized rhesus and cynomolgus monkeys. FdUrd disappearance from plasma was an apparent triexponential process with average half-lives of 0.5, 2, and 8 min; FUra disappearance was biphasic with average half-lives of 2 and 13 min. After FdUrd injection, FUra reached peak plasma concentrations of 15-30% of the initial FdUrd concentrations within 3 min, and then disappeared more slowly than FdUrd. Total FdUrd clearance fell from 105 to 73 to 56 ml/kg/min as the dose increased from 10 to 20 to 40 mg/kg. Metabolic clearance was about 85% of total clearance and fell similarly with increasing dosage. Total and metabolic FUra clearances were about 30% of FdUrd values at an equimolar dose. Renal FdUrd clearance exceeded glomerular filtration rate and was decreased by probenecid, indicating tubular secretion; renal FUra clearance was close to glomerular filtration rate. There was no apparent correlation between dose and renal clearance or volume of distribution. It was concluded that FdUrd, like FUra, is eliminated primarily by a dose-dependent process. The metabolic basis of the dosedependent kinetics remains to be determined. 0 1987 society for Experimental Biology and Medicine. 326

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Phosphorolysis of 5′-deoxy-5-fluorouridine in human plasma, serum and blood platelets

Meynial

Malet‐Martino

Lopez

et al. 1986

Journal of Pharmacy and Pharmacology

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During the course of the study of 5′‐deoxy‐5‐fluorouridine (5′dFUrd) plasma protein binding using 19F NMR spectroscopy, phosphorolytic cleavage of 5′dFUrd into 5‐fluorouracil (5FU) was observed. This transformation was due to the enzymatic content of residual blood cells present in plasma, since the percentage conversion of 5′dFUrd into 5FU was lower as the number of residual blood cells fell, and an ‘acellular’ plasma or a serum effected a negligible phosphorolyis of 5′dFUrd. As platelets were the contaminants of the plasma samples studied, and a concentrate of human platelets demonstrated a high phosphorolytic activity towards 5′dFUrd, it was concluded that these blood cells were responsible for the 5′dFUrd cleavage. Thymidine phosphorylase, being the only pyrimidine nucleoside phosphorylase in human platelets, is suggested by the present results to catalyse 5′dFUrd phosphorolysis and is therefore not as specific for 2′‐deoxyribonucleosides as has been reported.

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Thymidine Phosphorylase Activity in Plasma: A Cancer Marker or an Artifact of Ultrafiltration?

Cited by 3 publications

References 0 publications

Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells

Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells

Dose-Dependent Elimination of 5-Fluoro-2'-deoxyuridine in the Monkey

Phosphorolysis of 5′-deoxy-5-fluorouridine in human plasma, serum and blood platelets

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