Lack of effect of TP53 status on fluorodeoxyuridine-mediated radiosensitization.
Substantial evidence suggests that TP53 (also known as p53) status can influence the response of cells to chemotherapy and radiation. We wished to determine if TP53 function affected the response of cells to fluoropyrimidines and radiation, a combination used for tens of thousands of patients each year. To assess the role of TP53 in fluoropyrimidine-mediated radiosensitization, we carried out experiments using RKO parental cells (wild-type TP53) and RKO cells overexpressing mutant TP53 (which blocks TP53 function) or expressing E6 (which degrades TP53). We found that TP53 function had no effect on the ability of fluorodeoxyuridine to increase radiation sensitivity. These findings are consistent with the hypothesis that the late G(1)-phase checkpoint, which is mediated by TP53, is not crucial to radiosensitization. Rather, the ability of cells to progress in to S phase in the presence of the drug, which is independent of TP53, is more closely associated with increased radiation sensitivity.
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
T S
TS
Lawrence
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Burke
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Davis
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival; D003110:Colonic Neoplasms; D005467:Floxuridine / Q000494:pharmacology*; D006801:Humans; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000032:analysis; D016196:S Phase; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D005467:Floxuridine