TP53 and TP53-related genes associated with protection from apoptosis in the radioadaptive response |
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Authors: | Okazaki Ryuji Ootsuyama Akira Norimura Toshiyuki |
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Institution: | 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 |
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Abstract: | 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. |
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