TP53 and TP53-related genes associated with protection from apoptosis in the radioadaptive response.
We investigated the effect of administering priming low-dose radiation prior to high-dose radiation on the level of apoptosis and on the expression of TP53 and TP53-related genes in mouse splenocytes. The percentage of apoptotic cells was significantly lower in TP53(+/+) mice receiving priming radiation 2 to 168 h before the high-dose irradiation, compared to TP53(+/+) mice exposed to 2 Gy alone. In contrast, TP53(+/-) mice exhibited a reduced level of apoptosis only when priming was performed for 2 or 4 h prior to the high-dose irradiation. In TP53(+/+) mice, primed mice had higher TP53 expression than mice exposed to 2 Gy. Phospho-TP53 (ser15/18) expression was the highest in mice exposed to 2 Gy and intermediate in primed mice. Expression of p21 (CDKN1A) was higher in primed mice compared with mice exposed to 2 Gy. MDM2 expression remained at a high level in all mice receiving 2 Gy. Elevated phospho-ATM expression was observed only in mice exposed to 2 Gy. We conclude that TP53 plays a critical role in the radioadaptive response and that TP53 and TP53-related genes might protect cells from apoptosis through activation of the intracellular repair system.
Okazaki
Ryuji
R
Department of Radiation Biology and Health, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. ryuji-o@med.uoeh-u.ac.jp
Ootsuyama
Akira
A
Norimura
Toshiyuki
T
D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation; D016158:Genes, p53; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D011827:Radiation; D011836:Radiation Tolerance; D013154:Spleen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53