Lack of effect of TP53 status on fluorodeoxyuridine-mediated radiosensitization

Substantial evidence suggests that TP53 (also known as p53) status can infl uence the response of cells to chemotherapy and radiation. We wished to det ermine if TP53 function affected the response of cells to fluoropyrimidines and radiation, a combination used for lens of thousands of patients each y ear. To assess the role of TP53 in fluoropyrimidine-mediated radiosensitiza tion, we carried out experiments using RKO parental cells (wild-type TP53) and RKO cells overexpressing mutant TP53 (which blocks TP53 function) or ex pressing E6 (which degrades TP53), We found that TP53 function had no effec t on the ability of fluorodeoxyuridine to increase radiation sensitivity. T hese findings are consistent with the hypothesis that the late G(1)-phase c heckpoint, 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 inc reased radiation sensitivity. (C) 2000 by Radiation Research Society.