PMID: 8600090Mar 15, 1996Paper

PALA enhancement of bromodeoxyuridine incorporation into DNA increases radiation cytotoxicity to human ovarian adenocarcinoma cells

International Journal of Radiation Oncology, Biology, Physics
J L YangR L Capizzi

Abstract

N-(phosphonacetyl)-L-aspartic acid (PALA) is a transition- state inhibitor of L-aspartate transcarbamylase, which catalyses the biosynthesis of carbamyl-L-aspartate in the de novo pyrimidine biosynthetic pathway. 5-Bromodeoxyuridine (BrdUrd) is known to be a potent radiosensitizer of proliferating cells when it is incorporated into DNA. The experiments described herein were performed to test the hypothesis that depletion of cellular pyrimidine precursors by PALA may increase both the incorporation of BrdUrd into DNA and the sensitivity of these cells to the cytotoxic effect of radiation. The effect of PALA concentration and exposure time on the incorporation of BrdUrd into the DNA of exponentially growing BG-1 human ovarian carcinoma cells was determined. BG-1 cells exposed to the most effective PALA + BrdUrd treatment schedule were then irradiated to determine if PALA could enhance the radiosensitization already achieved by pretreatment with BrdUrd alone. A 72-h exposure to PALA (> or = 25 microM) delayed the growth of human ovarian adenocarcinoma BG-1 cells by 40% compared to that of the untreated control cells. Using a clonogenic assay, the IC50 for a 72-h PALA exposure was approximately 25 microM and the cell killing effici...Continue Reading

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Citations

Jan 31, 2004·International Journal of Radiation Oncology, Biology, Physics·Yongbiao LiShirley Lehnert
Nov 19, 2004·Radiation Research·S CecchiniD J Hunting

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