PMID: 8598364Mar 1, 1996Paper

Radiosensitization of pancreatic cancer cells by 2',2'-difluoro-2'-deoxycytidine

International Journal of Radiation Oncology, Biology, Physics
T S LawrenceD S Shewach

Abstract

We have reported that the deoxycytidine analog 2',2'difluoro-2'-deoxycytidine (dFdCyd) is a potent radiosensitizer of HT29 human colon cancer cells probably through its effects on intracellular deoxyribonucleotide (dNTP) pools. Because dFdCyd has activity against pancreatic cancer in clinical trials, we wished to determine if dFdCyd would radiosensitize human pancreatic cancer cells. We assessed the effect of dFdCyd on radiation sensitivity of two human pancreatic cancer cell lines, Panc-1 and BxPC-3. To begin to investigate the mechanism of sensitization, we determined the effect of dFdCyd on dNTP pools and cell cycle distribution. We found that dFdCyd produced radiation enhancement ratios of 1.7-1.8 under noncytotoxic conditions in both cell lines. Sensitization was not associated with intracellular levels of 2',2'-difluoro-2'-deoxycytidine triphosphate, the cytotoxic metabolite of dFdCyd, but occurred when dATP pools were depleted below the level of approximately 1 micromolar. Although both cell lines showed substantial cell cycle redistribution after drug treatment, the flow cytogram of the BxPC-3 cells would not, by itself, be anticipated to result in increased radiation sensitivity. These findings demonstrate that dFdCyd ...Continue Reading

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Citations

Jan 5, 2002·International Journal of Cancer. Journal International Du Cancer·Thomas M CardilloDavid V Gold
Jan 1, 1996·Investigational New Drugs·D S Shewach, T S Lawrence
Sep 13, 2007·Medical Oncology·Mustafa CengizIbrahim H Gullu
Oct 2, 2008·Cancer Chemotherapy and Pharmacology·Hee Man KimSeung Woo Park
May 9, 2008·International Journal of Clinical Oncology·Edgar Ben-Josef, Theodore S Lawrence
Mar 15, 2006·Current Gastroenterology Reports·Robert de W Marsh, Thomas George
Feb 18, 2004·International Journal of Radiation Oncology, Biology, Physics·Ralf WilkowskiVolker Heinemann
Jan 31, 2004·International Journal of Radiation Oncology, Biology, Physics·Mei ZhangKate Fife
Jun 1, 2005·International Journal of Radiation Oncology, Biology, Physics·Chris van BreeNicolaas A P Franken
Mar 24, 2004·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Jean-François RosierVincent Grégoire
Sep 29, 2000·Pharmacology & Therapeutics·G J PetersS P Ackland
Jun 29, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·M LopreviteA Ardizzoni
Sep 29, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·R Fietkau
Jun 6, 2000·International Journal of Radiation Oncology, Biology, Physics·M T FieldsT S Lawrence
Dec 1, 2001·International Journal of Radiation Oncology, Biology, Physics·A W BlackstockA Miller
Nov 13, 2001·International Journal of Radiation Oncology, Biology, Physics·A A YavuzF Ozdemir
May 15, 2002·International Journal of Radiation Oncology, Biology, Physics·Zvi SymonTheodore S Lawrence
Nov 7, 2002·International Journal of Radiation Oncology, Biology, Physics·Donald J BuchsbaumKevin P Raisch
Dec 31, 2002·International Journal of Radiation Oncology, Biology, Physics·Thomas B BrunnerRolf Sauer
Jun 28, 2003·International Journal of Radiation Oncology, Biology, Physics·Jean-Luc Van LaethemJean Closset
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Sep 6, 2003·International Journal of Radiation Oncology, Biology, Physics·Floris M WachtersHarm H Kampinga
Nov 25, 2003·International Journal of Radiation Oncology, Biology, Physics·Orazio CaffoEnzo Galligioni
Oct 25, 2003·International Journal of Radiation Oncology, Biology, Physics·Bea PauwelsFilip Lardon
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