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Published Online: 5 July 2004

A Balanced Deoxyribonucleoside Mixture Increased the Rate of DNA Incorporation of 5-[125I]Iodo-2′-deoxyuridine in Glioblastoma Cells

Publication: Cancer Biotherapy and Radiopharmaceuticals
Volume 18, Issue Number 1

Abstract

Administration of nucleotide mixtures has been shown to restore and sustain the proliferation of leukocytes and enterocytes. Since it has been suggested that cancer cells use exogenous nucleotides more efficiently than normal cells, we hypothesized that administration of nucleotide mixtures would also stimulate the proliferation of cancer cells, thereby increasing the number of cells targeted by the thymidine analog 5-[125I]iodo-2′-deoxyuridine ([125I]IUdR). We first evaluated the influence of different deoxyribonucleoside mixtures on the DNA incorporation of [125I]IUdR in 3 human glioblastoma cell lines. Results showed that a 4-h coincubation with a mixture of identical concentration (10 μM) of deoxyadenosine, deoxyuridine, deoxyguanosine and deoxycytidine (AUGC) increased by 8.5-, 6.2-, and 2.0-fold the rate of DNA incorporation of [125I]IUdR in exponentially growing LN229, U87 and U251 cells, respectively. Replacing deoxyuridine by thymidine (ATGC) reversed the effect of the mixture, whereas removing deoxyuridine allowed a mixture of 10 μM AGC to increase by 2.2-fold the rate of DNA incorporation of [125I]IUdR in LN229 cells. Furthermore, the rate of DNA incorporation of [125I]IUdR in LN229 and U87 cells was increased up to 19.9- and 9.4-fold, respectively, by extending the coincubation time with 10 μM AUGC to 9 h, and up to 40.9- and 26.8-fold by incubating confluent cells for 4 h with 10 μM AUGC. Flow cytometry analysis showed that exposure of confluent cells to AUGC increased the percentage of cells in S phase of the cell cycle. Thus, co-administration of a balanced deoxyribonucleoside mixture may improve the use of radiolabeled nucleotide analogs, such as [125I]IUdR, for the targeting of cancer cells.

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Published In

cover image Cancer Biotherapy and Radiopharmaceuticals
Cancer Biotherapy and Radiopharmaceuticals
Volume 18Issue Number 1February 2003
Pages: 7 - 16
PubMed: 12667304

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Published online: 5 July 2004
Published in print: February 2003

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Y M Dupertuis
Divisions of Nutrition and Nuclear Medicine, University Hospital of Geneva, 1211 Geneva 14, Switzerland
F Buchegger
Nuclear Medicine, University Hospital of Geneva, 1211 Geneva 14, Switzerland
C Pichard
Division of Nutrition, University Hospital of Geneva, 1211 Geneva 14, Switzerland

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