Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice.
Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice.
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p53 基因在小鼠基因毒性组织损伤凋亡修复中的作用。
DOI：
10.1269/jrr.43.s209
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发表时间：
2002
影响因子：
2
通讯作者：
T. Norimura
中科院分区：
文献类型：
--
作者：
F. Kato;H. Kakihara;N. Kunugita;A. Ootsuyama;T. Norimura
当DNA因暴露于少量辐射而受损时，它会通过先天机制有效地修复。然而，如果细胞损伤更广泛，DNA修复不能充分完成。为了阐明p53基因在凋亡组织修复中的作用，我们通过测量p53（+/+）和p53（-/-）小鼠体内T细胞受体（TCR）基因表达来评估体内辐射诱导体细胞突变的发生率。3gy γ辐照后，p53（+/+）小鼠的TCR突变频率（MF）高于对照组。然而，当小鼠以低剂量率暴露于3gy时，p53（+/+）小鼠的TCR MF没有增加，而p53（-/-）小鼠的TCR MF增加并保持升高，而p53（-/-）小鼠无法诱导细胞凋亡。在p53（+/+）小鼠中，TCR MF在高剂量率照射3gy后第9天达到峰值，随后逐渐下降，半衰期约为13天。然而，在p53（-/-）小鼠中，TCR MF的峰值水平并未随着时间的推移而显著下降。因此，辐照组织中致突变损伤的完全修复需要DNA修复和p53依赖性凋亡组织修复的结合。
When DNA is damaged by exposure to a small amount of radiation, it is repaired efficiently by innate mechanisms. However, if cellular damage is more extensive, DNA repair cannot be adequately completed. To clarify the role of the p53 gene in apoptotic tissue repair, the incidence of in-vivo radiation-induced somatic mutation was evaluated by measuring the T cell receptor (TCR) gene expression in p53(+/+) and p53(-/-) mice. After gamma-irradiation with 3 Gy, the TCR mutation frequency (MF) was higher in p53(+/+) mice than in the controls. However, when the mice were exposed to 3 Gy at a low dose rate, the TCR MF did not increase in the p53(+/+) mice, whereas it increased and remained elevated in p53(-/-) mice, which are unable to induce apoptosis. In p53(+/+) mice, the TCR MF peaked 9 days after gamma-irradiation with 3 Gy at a high dose rate, and then gradually decreased with a half-life of about 13 days. However, in p53(-/-) mice, the peak level of the TCR MF did not decline significantly with time. Hence, complete repair of mutagenic damage in irradiated tissues requires the integration of DNA repair and p53-dependent apoptotic tissue repair.