The effect of inhibition of cytidine deaminase by tetrahydrouridine on the utilization of deoxycytidine and 5 bromodeoxycytidine for deoxyribonucleic acid synthesis

G. M. Cooper, S. Greer

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27 Citations (Scopus)

Abstract

The effect of cytidine deaminase activity on the utilization of deoxycytidine and 5 bromodeoxycytidine for DNA synthesis in normal and neoplastic mouse tissues was investigated utilizing tetrahydrouridine to inhibit cytidine deaminase in vivo. Tetrahydrouridine increased approximately 3 fold the incorporation of deoxycytidine into the DNA of two transplantable lymphomas, a mammary adenocarcinoma, and bone marrow. The utilization of deoxycytidine for DNA synthesis was also increased by tetrahydrouridine in mouse testes, but not in the spleen or small intestine. The toxicity of 5 fluorodeoxycytidine was similarly increased by inhibition of cytidine deaminase. In contrast to the effect of tetrahydrouridine on deoxycytidine, the incorporation of 5 bromodeoxycytidine into DNA was decreased approx 70% by inhibition of cytidine deaminase with tetrahydrouridine. This suggests that the incorporation of 5 bromodeoxycytidine into DNA proceeds mainly by deamination of the nucleoside to 5 bromodeoxyuridine, followed by phosphorylation to 5 bromodeoxyuridylate, rather than the alternative pathway proceeding by phosphorylation of 5 bromodeoxycytidine to 5 bromodeoxycytidylate, followed by deamination of the nucleotide to 5 bromodeoxyuridylate.

Original languageEnglish
Pages (from-to)698-703
Number of pages6
JournalMolecular Pharmacology
Volume9
Issue number6
StatePublished - Dec 1 1973
Externally publishedYes

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Bromodeoxycytidine
Tetrahydrouridine
Cytidine Deaminase
Deoxycytidine
DNA
Deamination
Phosphorylation
Bromodeoxyuridine
Nucleosides
Small Intestine
Testis
Lymphoma
Adenocarcinoma
Breast
Spleen
Nucleotides
Bone Marrow

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "The effect of inhibition of cytidine deaminase by tetrahydrouridine on the utilization of deoxycytidine and 5 bromodeoxycytidine for deoxyribonucleic acid synthesis",
abstract = "The effect of cytidine deaminase activity on the utilization of deoxycytidine and 5 bromodeoxycytidine for DNA synthesis in normal and neoplastic mouse tissues was investigated utilizing tetrahydrouridine to inhibit cytidine deaminase in vivo. Tetrahydrouridine increased approximately 3 fold the incorporation of deoxycytidine into the DNA of two transplantable lymphomas, a mammary adenocarcinoma, and bone marrow. The utilization of deoxycytidine for DNA synthesis was also increased by tetrahydrouridine in mouse testes, but not in the spleen or small intestine. The toxicity of 5 fluorodeoxycytidine was similarly increased by inhibition of cytidine deaminase. In contrast to the effect of tetrahydrouridine on deoxycytidine, the incorporation of 5 bromodeoxycytidine into DNA was decreased approx 70{\%} by inhibition of cytidine deaminase with tetrahydrouridine. This suggests that the incorporation of 5 bromodeoxycytidine into DNA proceeds mainly by deamination of the nucleoside to 5 bromodeoxyuridine, followed by phosphorylation to 5 bromodeoxyuridylate, rather than the alternative pathway proceeding by phosphorylation of 5 bromodeoxycytidine to 5 bromodeoxycytidylate, followed by deamination of the nucleotide to 5 bromodeoxyuridylate.",
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AU - Greer, S.

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N2 - The effect of cytidine deaminase activity on the utilization of deoxycytidine and 5 bromodeoxycytidine for DNA synthesis in normal and neoplastic mouse tissues was investigated utilizing tetrahydrouridine to inhibit cytidine deaminase in vivo. Tetrahydrouridine increased approximately 3 fold the incorporation of deoxycytidine into the DNA of two transplantable lymphomas, a mammary adenocarcinoma, and bone marrow. The utilization of deoxycytidine for DNA synthesis was also increased by tetrahydrouridine in mouse testes, but not in the spleen or small intestine. The toxicity of 5 fluorodeoxycytidine was similarly increased by inhibition of cytidine deaminase. In contrast to the effect of tetrahydrouridine on deoxycytidine, the incorporation of 5 bromodeoxycytidine into DNA was decreased approx 70% by inhibition of cytidine deaminase with tetrahydrouridine. This suggests that the incorporation of 5 bromodeoxycytidine into DNA proceeds mainly by deamination of the nucleoside to 5 bromodeoxyuridine, followed by phosphorylation to 5 bromodeoxyuridylate, rather than the alternative pathway proceeding by phosphorylation of 5 bromodeoxycytidine to 5 bromodeoxycytidylate, followed by deamination of the nucleotide to 5 bromodeoxyuridylate.

AB - The effect of cytidine deaminase activity on the utilization of deoxycytidine and 5 bromodeoxycytidine for DNA synthesis in normal and neoplastic mouse tissues was investigated utilizing tetrahydrouridine to inhibit cytidine deaminase in vivo. Tetrahydrouridine increased approximately 3 fold the incorporation of deoxycytidine into the DNA of two transplantable lymphomas, a mammary adenocarcinoma, and bone marrow. The utilization of deoxycytidine for DNA synthesis was also increased by tetrahydrouridine in mouse testes, but not in the spleen or small intestine. The toxicity of 5 fluorodeoxycytidine was similarly increased by inhibition of cytidine deaminase. In contrast to the effect of tetrahydrouridine on deoxycytidine, the incorporation of 5 bromodeoxycytidine into DNA was decreased approx 70% by inhibition of cytidine deaminase with tetrahydrouridine. This suggests that the incorporation of 5 bromodeoxycytidine into DNA proceeds mainly by deamination of the nucleoside to 5 bromodeoxyuridine, followed by phosphorylation to 5 bromodeoxyuridylate, rather than the alternative pathway proceeding by phosphorylation of 5 bromodeoxycytidine to 5 bromodeoxycytidylate, followed by deamination of the nucleotide to 5 bromodeoxyuridylate.

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