The role of p53 in protection of radiation mutagenesis

p53 在辐射诱变保护中的作用

• 批准号: 15201013
• 负责人: NORIMURA Toshiyuki
• 金额: $ 18.05万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15201013/
• 关键词: p53 gene; mutation; p53-dependent apoptosis; tissue repair; radiation; dose-rate dependence; genomic instability

The major risks of low-dose radiation are mutagenesis, teratogenesis and carcinogenesis. All three have been shown (experimentally) to approach zero risk with decreasing dose rate, demonstrating the critical contribution of DNA repair at low dose-rate irradiation. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. The influence of p53 on the radiation-induce elevation of T-cell receptor (TCR) variant fractions was examined in splenic T lymphocytes of p53-proficient and -deficient mice.(1)After acute gamma-irradiation with 3 Gy (@ 61 Gy/h), the TCR variant fraction was higher than the control level. However, when an equal dose of 3 Gy was given but at a lower dose-rate of 0.07 Gy/h, the fraction of TCR variants did not increase at all for p53(+/+) mice, whereas the same dose of 3 Gy remained mutagenic for p53(-/-) mice, which are unable to carry out p53-dependent apoptosis.(2)Initially, the TCR variant fraction increased rapidly and reached its maximum level at 9 days after irradiation before decreasing gradually. In p53(+/+) and p53(+/-) mice, the TCR variant fraction fell to normal background levels at 16 and 20 weeks of age, respectively. 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 p53(+/+) mice and after 44 weeks of age in the irradiated p53(+/-) mice. This delayed increase in TCR variants after irradiation is due to a reduction in p53-dependent apoptosis.These results indicate that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rate.

低剂量辐射的主要风险是诱变、致畸和致癌。所有这三个已被证明（实验）接近零风险，降低剂量率，证明了在低剂量率照射的DNA修复的关键贡献。然而，DNA修复并不完美。除了DNA修复，肯定还有其他防御机制。研究了p53对辐射诱导的T细胞受体（TCR）变体组分升高的影响。（1）3戈伊（@61戈伊/h）急性γ射线照射后，TCR变异体比例高于对照组。然而，当给予相等剂量的3戈伊但以0.07戈伊/h的较低剂量率时，p53（+/+）小鼠的TCR变体的分数根本没有增加，而相同剂量的3戈伊对p53（-/-）小鼠仍具有致突变性，其不能进行p53依赖性细胞凋亡。（2）TCR变异体比例在照射初期迅速上升，照射后9d达到最大值，随后逐渐下降。在p53（+/+）和p53（+/-）小鼠中，TCR变体分数分别在16和20周龄时降至正常背景水平。在长的平坦期之后，在照射的p53（+/+）小鼠中在72周龄之后和在照射的p53（+/-）小鼠中在44周龄之后发现TCR变体的分数显著再增加。辐射后TCR变异的延迟增加是由于p53依赖性细胞凋亡的减少，这些结果表明，p53基因对于低剂量或剂量率辐射风险的阈值效应是不可或缺的。

项目成果

Role of p53 gene in genetic instability induced by ionizing radiation

p53基因在电离辐射诱导的遗传不稳定性中的作用

• 发表时间: 2005
• 期刊: International Congress Series 1276
• 作者: Uehara;K.;K.Goto;T.Kobayashi;A.Kojima;T.Akema;T.Sugiura;S.Yamada;Y.Ohira;T.Yoshioka;H.Aoki.;K.IGARI
• 通讯作者: K.IGARI

欅田 尚樹: "放射線誘発突然変異の修復とp53遺伝子依存性アポトーシス"放射線生物研究. 38・4. 361-369 (2003)

Naoki Keyakita：“辐射诱导突变的修复和p53基因依赖性细胞凋亡”放射生物学研究38・4（2003）。

Increased radiosensitivity of splenic T lymphocytes in pregnant mice

妊娠小鼠脾脏 T 淋巴细胞放射敏感性增加

• 发表时间: 2005
• 期刊: International Congress Series 1276
• 作者: Hiroaki Yamajo;Hiroshi Saruwatari;Tomoya Takatani;Tsuyoki Nishikawa;Kiyohiro Shikano;Y.IGARI
• 通讯作者: Y.IGARI

体細胞における突然変異

体细胞突变

• 发表时间: 2006
• 期刊: エネルギー 39・3
• 作者: M.Takeuchi;H.Okochi;M.Igawa;土井正;法村 俊之
• 通讯作者: 法村 俊之

法村 俊之: "低線量・低線量率放射線による生物影響発現(大西武雄監修) 3-2-2.突然変異誘発の線量率効果"(株)アイプリコム. 62-64 (2003)

焰敏之：“由于低剂量/低剂量率辐射引起的生物效应的表达（由大西武夫监督）3-2-2.诱变的剂量率效应”Ipricom Co., Ltd. 62-64 (2003)