PMID: 3759575Aug 1, 1986Paper

Sensitization to X ray by 5-chloro-2'-deoxycytidine co-administered with tetrahydrouridine in several mammalian cell lines and studies of 2'-chloro derivatives

International Journal of Radiation Oncology, Biology, Physics
L M Perez, S B Greer

Abstract

5-Chloro-2'-deoxycytidine (CldC) + tetrahydrouridine (H4U) sensitizes mammalian cells (HEp-2, RIF-1, S-180) to X ray. This sensitization, as demonstrated previously with HEp-2 cells, is heightened when cells are pre-incubated with inhibitors of pyrimidine synthesis. CHO cells, which intrinsically lack both cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD), are sensitized to X ray by 5-chlorodeoxyuridine (CldU) but display no significant sensitization with CldC + H4U. The presence and level of these deaminases appears to correlate with X ray sensitization in cell culture. From experiments in cell culture, it can be inferred that one pathway of conversion, deoxycytidine kinase----dCMPD, or CD----thymidine kinase, may be sufficient for metabolizing CldC to a radiosensitizer. However, if both pathways are blocked, as in CHO cells, no X ray sensitization results. In addition to HEp-2 cells, which are extremely elevated in both CD and dCMPD activities, we have examined the sensitization of S-180 and RIF-1 cells to X ray by CldC + H4U. Both cell lines possess an enzymatic profile consistent with their sensitization to X ray by CldC + H4U. Dose enhancement ratios of 1.5 to 1.9 for cells treated with CldC + H4U and ratios of...Continue Reading

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Citations

May 1, 1989·International Journal of Radiation Oncology, Biology, Physics·T L PhillipsJ B Mitchell
Nov 6, 2002·Biochemical Pharmacology·JodiAnne T HaleJohn J McCormack
Jan 1, 1997·Acta Oncologica·P A CouckeR O Mirimanoff
Jan 1, 1990·Critical Reviews in Oncology/hematology·C N Coleman, A T Turrisi
Oct 1, 1990·Journal of Neuroendocrinology·M Fagan, R D Andrew
Dec 12, 2001·Current Problems in Cancer·M M PoggiJ B Mitchell
Aug 1, 1990·International Journal of Radiation Oncology, Biology, Physics·O SantosS B Greer

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