Okazaki, R., Ootsuyama, A. and Norimura, T. TP53 and TP53-Related Genes Associated with Protection from Apoptosis in the Radioadaptive Response. Radiat. Res. 167, 51–57 (2007).
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.