Effect of p53 overexpression on radiation sensitivity of human colon cancer cells.
Substantial controversy surrounds our understanding of the effect of p53 status on radiation sensitivity. To assess directly the role of p53 expression on radiation sensitivity, we chose a conditional expression system using a temperature-sensitive murine p53 that permitted each cell line to act as its own control. We found that the conditional expression of wild type p53 induced cell death (both apoptotic and nonapoptotic), changes in cell cycle distribution (arrest in G1 and G2, which resulted in a marked depletion of S-phase cells and an increase in the fraction of cells in G2), and an increase in the radiation resistance of G1 cells. These counterbalancing effects resulted in no significant effect on overall radiosensitivity. These findings demonstrate that wild type p53 function can produce a variety of effects that can modulate radiation sensitivity and may explain why p53 status alone has not been a strong predictor of radiosensitivity.
Zellars
R C
RC
Department of Radiation Oncology, University of Michigan, Ann Arbor 48109-0582, USA.
Naida
J D
JD
Davis
M A
MA
Lawrence
T S
TS
D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D016923:Cell Death; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D019073:HT29 Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D011237:Predictive Value of Tests; D011836:Radiation Tolerance / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53