Positive interactive radiosensitization observed in vitro with the combination of two nucleoside analogs (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC) and iododeoxyuridine (IdUrd).
[en] (E)-20-Deoxy-20-(fluoromethylene) cytidine (FMdC), an inhibitor of ribonucleotide diphosphate reductase (RR), is a potent radiation-sensitiser acting through alterations in the deoxyribonucleoside triphosphate (dNTP) pool in the de novo pathway to DNA
synthesis. The activity of thymidine kinase (TK), a key enzyme in the ‘salvage pathway’, is known to increase in response to a lowering of dATP induced by FMdC. Nucleoside analogues such as iododeoxyuridine (IdUrd) are incorporated into DNA after phosphorylation by TK. Radiation sensitisation by IdUrd depends on IdUrd incorporation. Therefore, we have investigated the radiosensitising effect of the combination of FMdC and IdUrd on WiDr (a human colon cancer cell-line) and compared it to the effect of either drug alone. We analysed the effects of FMdC and IdUrd on the dNTP pools by high-performance liquid chromatography, and measured whether the incorporation of IdUrd was increased by FMdC using a [125I]-IdUrd incorporation assay. The combination in vitro yielded radiation-sensitiser enhancement ratios of >2, significantly higher than those observed with FMdC or IdUrd alone. Isobologram analysis of the combination indicated a supra-additive effect. This significant increase in radiation sensitivity with the combination of FMdC and IdUrd could not be explained by changes in the dNTP pattern since the addition of IdUrd to FMdC did not further reduce the dATP. However, the increase in the radiation sensitivity of WiDr cells might be due to increased incorporation of IdUrd after FMdC treatment. Indeed, a specific and significant incorporation of IdUrd into DNA could be observed with the [125I]-IdUrd incorporation assay in the presence of 1 lM unlabelled IdUrd when combined with FMdC treatment. 2004 Elsevier Ltd. All rights reserved.
Disciplines :
Hematology Oncology
Author, co-author :
Coucke, Philippe ; Department of Radiation Oncology, Laboratory of Radiation Biology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Cottin, E
Azria, D
Martineau, P
Adamer, F
Decosterd, L-A
Buchegger, F
Do, H-P
Language :
English
Title :
Positive interactive radiosensitization observed in vitro with the combination of two nucleoside analogs (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC) and iododeoxyuridine (IdUrd).
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Gregoire V., Hittelman W.N. Nucleoside analogs as radiosensitizing agents. Cheson B.D., Keating M.J., Plunkett W. Nucleoside analogs in cancer therapy. 1997;315-358 Marcel Dekker, New York
Coucke P.A., Decosterd L.A., Li Y-X., Cottin E., Chen X., Sun L-Q., et al. The ribonucleoside diphosphate reductase inhibitor (E)-2. ′ -deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro Cancer Res. 59:1999;5219-5226
Decosterd L.A., Cottin E., Chen X., Lejeune F., Mirimanoff R.O., Biollaz J., et al. Simultaneous determination of deoxyribonucleoside in the presence of ribonucleoside triphosphates in human carcinoma cells by high-performance liquid chromatography. Anal. Biochem. 270:1999;59-68
Kassis A.I., Guptill W.E., Taube R.A., Adelstein S.J. Radiotoxicity of 5-[125I]iodo-2. ′ -deoxyuridine in mammalian cells following treatment with 5-fluoro-2 ′ deoxyuridine J. Nucl. Biol. Med. 35(3):1991;167-173
Breitman T.R. The feedback inhibition of thymidine kinase. Biochim. Biophys. Acta. 67:1963;153-158
Fischer P.H., Vazquez-Padua M.A., Reznikoff C.A., Ratschan W.J. Preferential stimulation of iododeoxyuridine phosphorylation by 5. ′ -aminothymidine in human bladder cancer cells in vitro Cancer Res. 46:1986;4522-4526
Weber G. Biochemical strategy of cancer cells and the design of chemotherapy. G.H.A. Clowes Memorial Lecture. Cancer Res. 43:1983;3466-3492
Steel G.G., Peckham M.J. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int. J. Radiat. Oncol. Biol. Phys. 5:1979;85-91
Steel G.G. Terminology in the description of drug-radiation interactions. Int. J. Radiat. Oncol. Biol. Phys. 5:1979;1145-1150
Kano Y., Ohnuma T., Okano T. Effects of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture. Cancer Res. 48:1988;351-356
Xiao W.H., Dupertuis Y., Mermillod B., Sun L-Q., de Tribolet N., Buchegger F. Unlabelled iododeoxyuridine increases the cytotoxicity and incorporation of 125I-iododeoxyuridine in 2 human glioblastoma cell lines. Nucl. Med. Commun. 21:2000;947-953
Dupertuis Y., Xiao W-H., De Tribolet N., Pichard C., Slosman D.O., Bischof-Delaloye A., et al. Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas. Eur. J. Nucl. Med. 29:2002;499-505
Phillips T.L., Bodell W.J., Uhl V., Ross G.Y., Rasmussen J., Mitchell J.B. Correlation of exposure time, concentration and incorporation of IdUrd in V-79 cells with radiation response. Int. J. Radiat. Oncol. Biol. Phys. 16:1989;1251-1255
Schultz C., Gaffney D., Lindstrom M.J., Kinsella T.J. Iododeoxyuridine radiosensitization of human glioblastoma cells exposed to acute and chronic gamma irradiation; mechanistic implications and clinical relevance. Cancer J. Sci. Am. 1:1995;151-161
Kuo M.L., Kinsella T.J. Expression of ribonucleotide reductase after ionizing irradiation in human cervical carcinoma cells. Cancer Res. 58:1998;2245-2252
Friedberg E.C., Walker G.C., Siede W. DNA repair and mutagenesis. 1995;American Society for Microbiology, Washington, DC. p. 6-14
Reichard P. Interactions between deoxyribonucleotide and DNA synthesis. Annu. Rev. Biochem. 57:1988;349-374
Sun L-Q., Li Y.X., Guillou L., Mirimanoff R-O., Coucke P.A. Antitumor and radiosensitizing effects of (E)-2. ′ -deoxy-(fluoromethylene) cytidine, a novel inhibitor of ribonucleoside diphosphate reductase, on human colon carcinoma xenografts in nude mice Cancer Res. 57:1997;4023-4028
Sun L-Q., Li Y-X., Guiilou L., Coucke P.A. (E)-2. ′ -deoxy-(fluoromethylene)cytidine potentiates radioresponse of two human solid tumor xenografts Cancer Res. 58:1998;5411-5417
Kinsella T.J., Vielhuber K.A., Kunugi K.A., Schuppo J., Davis T.W., Sands H. Preclinical toxicity and efficacy study of a 14-day schedule of oral 5-iodo-2-pyrimidinone-2. ′ -deoxyribose as a prodrug for 5-iodo-2 ′ -deoxyuridine radiosensitization in U251 human glioblastoma xenografts Clin. Canc. Res. 6:2000;1468-1475
Kinsella T.J., Schupp J.E., Davis T.W., Berry S.E., Hwang H-S., Warren K., et al. Preclinical study of the systemic toxicity and pharmacokinetics of 5-iodo-2-deoxypyrimidinone-2. ′ -deoxyribose as a radiosensitizing prodrug in two, non-rodent animal species. Implications for phase I study design Clin. Canc. Res. 6:2000;3670-3679
Herman J., Umar A., Polyak K., Graff J., Ahuja N., Markowitz S., et al. Incidence and functional consequences of hMLH1 promoter hypermerthylation in colorectal carcinoma. Proc. Natl. Acad. Sci. USA. 95:1998;6870-6875
Schultz C., Gaffney D., Lindstrom M.J., Kinsella T.J. Iododeoxyuridine radiosensitization of human glioblastoma cells exposed to acute and chronic gamma irradiation: mechanistic implications and clinical relevance. Cancer J. Sci. Am. 1:1995;151-161
Fink D., Aebi S., Howell S. The role of DNA mismatch repair in drug resistance. Clin. Cancer Res. 4:1998;1-6
Lage H., Dietel M. Involvement of the DNA mismatch repair system in antineoplastic drug resistance. J. Cancer Res. Clin. Oncol. 125:1999;156-165
Berry S.E., Davis T.W., Schupp J.E., Hwang H-S., de Wind N., Kinsella T.J. Selective radiosensitization of drug-resistant MutS homologue-2 (MSH2) mismatch repair deficient cells by halogenated thymidine (dThd) analogues: MSH2 mediated dThd analogue DNA levels and the differential cytotoxicity and cell cycle effects of the dThd analogues and 6-thioguanine. Cancer Res. 60:2000;5773-5780
Uhl V., Phillips T.L., Ross G.Y., Bodell W.J., Rasmussen J. Iododeoxyuridine incorporation and radiosensitization in three human tumor cell lines. Int. J. Radiat. Oncol. Biol. Phys. 22:1992;489-494
Lawrence T.S., Davis M.A., Maybaum J., Stetson P.L., Ensminger W.D. Modulation of iododeoxyuridine-mediated radiosensitization by 5-fluorouracil in human colon cancer cells. Int. J. Radiat. Oncol. Biol. Phys. 22:1992;499-503
Miller E.M., Kunugi K.A., Kinsella T.J. Effects of 5. ′ -aminothymidine and leucovorin on radiosensitisation by iododeoxuridine in human colon cancer cells Clin. Cancer Res. 1:1995;407-416
Kinsella T.J., Glennon M.C., Kunugi K.A., Lindstrom M.J. In vivo modulation of iododeoxyuridine metabolism and incorporation into cellular DNA by 5. ′ -amino-5 ′ -deoxythymidine in normal mouse tissues and two human colon cancer xenografts Clin. Cancer Res. 2:1996;981-989
Li Y-X., Sun L-Q., Weber-Johnson K., Paschoud N., Coucke P.A. Potentiation of cytotoxicity and radiosenitizatrion of (E)-2. ′ -deoxy-(fluoromethylene)cytidine by pentoxifylline in vitro Int. J. Cancer. 80:1999;155-160
Coucke PA, Cottin E, Decosterd LA, Azria D, Martineau P, Decosterd LA. Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside triphosphate pool by (E)-2′-deoxy-(fluoromethylene)cytidine (FMdC) and zidovudine (AZT) results in increased radiosensitivity in vitro [in preparation]
McGinn C.J., Kunugi K.A., Tutsch K.D., Feieraband C., Alberti D., Lindstrom M.J., et al. Leucovorin modulation of 5-iododeoxyuridine radiosensitization: a phase I study. Clin. Cancer Res. 2:1996;1299-1305
Prusoff W.H., Chang P.K. Regulation of thymidine kinase activity by 5-iodo-2. ′ -deoxyuridine-5 ′ -triphosphate and deoxythymidine-5 ′ -triphosphate Chem. Biol. Interact. 1:1969-1970;285-299
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.