Igari, K., Igari, Y., Okazaki, R., Kato, F., Ootsuyama, A. and Norimura, T. The Delayed Manifestation of T-Cell Receptor (TCR) Variants in X-Irradiated Mice Depends on Trp53 Status. Radiat. Res. 166, 55–60 (2006).

The influence of Trp53 on the radiation-induced elevation of T-cell receptor (TCR) variant fractions was examined in splenic T lymphocytes of Trp53-proficient and -deficient mice. Wild-type Trp53 ^/ , heterozygous Trp53 ^/− and null Trp53^−/− mice were exposed to 3 Gy of X rays at 8 weeks of age. The fraction of TCR-defective variants was measured at various times after irradiation. Initially, the TCR variant fraction increased rapidly and reached its maximum level at 9 days after irradiation before decreasing gradually. In Trp53 ^/ and Trp53 ^/− mice, the TCR variant fraction fell to normal background levels at 16 and 20 weeks of age, respectively. In contrast, the TCR variant fraction of Trp53^−/− mice failed to decrease to background levels during the observation period. Baseline levels were then maintained for approximately 60 weeks in the Trp53 ^/ mice and approximately 40 weeks in the Trp53 ^/− mice. After the long flat period, a significant re-increase in the fraction of TCR variants was found after 72 weeks of age in the irradiated Trp53 ^/ mice and after 44 weeks of age in the irradiated Trp53 ^/− mice. Measurement of the fraction of apoptotic cells in the spleen and thymus 4 h after X irradiation at these ages in Trp53 ^/ and Trp53 ^/− mice demonstrated a reduction in apoptosis in the irradiated mice compared to the nonirradiated mice. This suggests that the delayed increase in TCR variants after irradiation is due to a reduction in Trp53-dependent apoptosis.