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

前言：我们用P53(-/-)小鼠(KO)、P53(/-)小鼠(异种)和P53(/)小鼠(WARD)研究了P53基因对辐射致畸的保护机制。在野生鼠中，p53依赖和独立的DNA修复机制共同修复DNA损伤，然后通过低剂量率辐射(LDR)后依赖于P53的细胞凋亡有效地去除不可修复的损伤细胞。因此，致畸率保持在控制水平。另一方面，在KO小鼠中，P53非依赖的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下降到对照水平。(加藤F等人)艾尔内部J.Radiat。比奥尔。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，我们利用与上面相同的小鼠，研究了p53基因是否具有去除DAMA…的机制更多的GES不仅通过DNA修复机制，而且在辐射致癌过程中也通过细胞凋亡来实现。在野鼠中，如果几乎完全在重复的LDR上进行DNA损伤的修复和通过凋亡去除损伤细胞，癌症可能不会发生。但在相同的实验条件下，如果KO小鼠发生肿瘤，则认为辐射致癌过程存在一个阈值剂量。每周三次用贝塔射线照射小鼠的背部，直到肿瘤发生或在小鼠的整个生命周期内。贝塔射线源：90；90；Y盘，1.85GBq，15Gy/min。I组：2.SGy/d。II组：5Gy日一次。结果：在KO小鼠中未发现肿瘤的发生。在杂交鼠中，I组和II组的肿瘤发生率分别为8/21和25/45，在野生鼠中，I组和II组的肿瘤发生率分别为2/8和6/33，肿瘤的出现时间比异种鼠晚约150天。在异种小鼠中，17/26的肿瘤有P53杂合性缺失，但没有突变。在野生型小鼠中，7/9的肿瘤有突变，1/7的肿瘤有LOH。结论：P53基因的存在状态对肿瘤的发病时间和发病率有明显影响。P53基因的变异类型可能因P53基因的存在状态而不同

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