Evidence that individual variations in TP53 and CDKN1A protein responsiveness are related to inherent radiation sensitivity.
We tested the hypothesis that individual variations in the induction of the TP53 tumor suppressor protein by radiation are related to inherent radiosensitivity. Thirty-two fibroblast cell strains were examined. Radiosensitivity was measured by a clonogenic survival assay. The induction of TP53 and its transcriptionally activated CDKN1A (p21) protein were studied by Western blotting 3 h after a single dose of 5 Gy. The relative cell culture age, as determined by the colony size distribution, was studied as a confounding factor. Survival curves showed wide range of radiosensitivity. The surviving fraction at 2 Gy (SF2) ranged between 0.02 and 0.49 (mean = 0.29, SD = 0.13). TP53 induction ranged between 1.28 and 2.34 (mean = 1.80, SD = 0.31). CDKN1A showed a wider induction (1.09-4.05, mean = 2.33, SD = 0.78). Positive correlations were observed between SF2 and TP53 induction (R(2) = 0.62, P < 0.001) and CDKN1A (R(2) = 0.64, P < 0.001). No correlation with the colony size distribution was observed. In conclusion, these results suggest that the individual variations in radiosensitivity and in the level of induction of TP53 (and consequently CDKN1A) are congruent, irrespective of the genetic background of these nontransformed fibroblasts. It is postulated that underlying mechanisms culminating in a stronger TP53 induction lead to higher survival, presumably due to more efficient repair of radiation-induced damage.
Alsbeih
G
G
Radiation Biology Laboratory, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. galsbeih@kfshrc.edu.sa
Torres
M
M
Al-Harbi
N
N
Al-Buhairi
M
M
D015153:Blotting, Western; D018929:Cell Culture Techniques / Q000379:methods; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011827:Radiation; D011836:Radiation Tolerance; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53