The delayed manifestation of T-cell receptor (TCR) variants in X-irradiated mice depends on Trp53 status.
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.
Igari
Kazuyuki
K
Department of Radiation Biology and Health, School of Medicine, University of Occupational and Environmental Health, Japan.
Igari
Yuka
Y
Okazaki
Ryuji
R
Kato
Fumio
F
Ootsuyama
Akira
A
Norimura
Toshiyuki
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014916:Whole-Body Irradiation; D014965:X-Rays
D011948:Receptors, Antigen, T-Cell; D016159:Tumor Suppressor Protein p53