Infulence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation

p53 对重复 β 辐射诱导小鼠皮肤肿瘤的影响

• 批准号: 16310046
• 负责人: OOTSUYAMA Akira
• 金额: $ 4.49万
• 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 (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310046/
• 关键词: P53 gene; KO mouse; Beta-irradiation; repetitive irradiation; skin cancer; radiation carcinogenesis

Introduction: We studied about a protection mechanism of p53 gene against a radiation induced teratogenesis using p53 (-/-) mice (KO), a p53 (+/-) mice (hetero) and a p53 (+/+) mice (wild). In wild mice, p53 dependent and independent DNA repair mechanisms restore DNA damages together, and then unrestorable damage cells are removed by p53 dependent apoptosis effectively after low dose rate radiation (LDR). Therefore the teratogenic rate keeps control level. On the other hand, in a KO mice, p53 independent DNA repair mechanism works, but p53 dependent DNA repair mechanism and apoptosis don' t work. So the teratogenic rate does not decrease to a control level at even low dose rate irradiation in KO mice. (Kato F, et. al. Int. J. Radiat. Biol. 77, 13-, 2001) In the DNA damage after LDR, it is thought there are similar mechanisms in processes of carcinogenesis and teratogenesis. In this study, with the mice same as an above it, we investigate whether a p53 gene has mechanisms to remove dama … More ges by not only DNA repair mechanism but also apoptosis on radiation carcinogenesis process. In wild mice, if a repair of DNA damages and removing of damage cells by apoptosis are almost completely performed on repetitive LDR, the cancer might not occur. But under the same experimental condition, if the cancer occurs in KO mice, it is thought there is a threshold dose on radiation carcinogenesis process.Method: Seven weeks old mice were used. The backs of the mice were irradiated with beta-rays three times a week until occurrence of tumor or throughout the life of the mice. Beta-rays source: <90>Sr^-^<90>Y disk, 1.85GBq, 15Gy/min. Group I: 2.SGy/day. Group II: 5Gy/day. P53 genes extracted from the tumors were analyzed about LOH and mutation.Results: In KO mice, we did not found occurrence of tumor. In hetero mice, we found 8/21 and 25/45 of tumor incidence in Group I and Group II. In wild mice, we found 2/8 and 6/33 of tumor incidence in Group I and Group II, and appearance time of the tumors was about 150days later than that of hetero mice. In hetero mice, 17/26 of tumors had LOH of p53 but had not mutations. In wild mice, 7/9 of tumors had mutations and 1/7 of tumor had LOH.Conclusion: An existence state of a p53 gene affects the tumor-causing time and incidence obviously. Types of variation of a p53 gene may be different by an existence state of a p53 gene Less

简介：我们使用p53（-/-）小鼠（KO）、p53（+/-）小鼠（异种）和p53（+/+）小鼠（野生）研究了p53基因针对辐射诱导畸胎的保护机制。在野生小鼠中，p53依赖性和独立性DNA修复机制共同修复DNA损伤，然后低剂量率辐射（LDR）后，p53依赖性细胞凋亡有效地去除不可恢复的损伤细胞。因此致畸率保持在控制水平。另一方面，在KO小鼠中，p53独立的DNA修复机制起作用，但p53依赖的DNA修复机制和细胞凋亡不起作用。因此，即使在低剂量率照射下，KO 小鼠的致畸率也不会降低至对照水平。 (Kato F, et. al. Int. J. Radiat. Biol. 77, 13-, 2001) 在LDR后的DNA损伤中，人们认为在致癌和致畸过程中存在相似的机制。在这项研究中，我们以与上述相同的小鼠为对象，研究p53基因是否具有通过DNA修复机制和放射性致癌过程中的细胞凋亡来消除dama ... More ges的机制。在野生小鼠中，如果DNA损伤的修复和通过细胞凋亡去除损伤细胞几乎完全在重复的LDR上进行，则癌症可能不会发生。但在相同的实验条件下，如果KO小鼠发生癌症，则认为放射致癌过程存在阈值剂量。方法：使用7周龄的小鼠。每周用β射线照射小鼠背部3次，直至肿瘤发生或终生。 β射线源：<90>Sr^-^<90>Y盘，1.85GBq，15Gy/min。第一组：2.SGy/天。第二组：5Gy/天。从肿瘤中提取的P53基因进行LOH和突变分析。结果：在KO小鼠中，我们没有发现肿瘤的发生。在异种小鼠中，我们发现 I 组和 II 组的肿瘤发生率分别为 8/21 和 25/45。在野生小鼠中，我们发现I组和II组的肿瘤发生率分别为2/8和6/33，且肿瘤出现时间比异种小鼠晚约150天。在异种小鼠中，17/26 的肿瘤具有 p53 LOH，但没有突变。野生小鼠中7/9的肿瘤发生突变，1/7的肿瘤发生LOH。结论：p53基因的存在状态对肿瘤的发生时间和发生率影响明显。 p53基因的变异类型可能因p53基因的存在状态而不同。

项目成果

β線による皮膚発がんの発生率と発生時期はp53遺伝子の存在状態に依存

β 射线引起的皮肤癌的发病率和发生时间取决于 p53 基因的存在。

• 发表时间: 2007
• 作者: 大津山彰;岡崎龍史;法村俊之
• 通讯作者: 法村俊之

Influence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation

p53 对重复 β 射线照射诱发小鼠皮肤肿瘤的影响

• 发表时间: 2007
• 作者: Ootsuyama A;Okazaki R;Norimura T.
• 通讯作者: Norimura T.