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Relationship between DNA Repair and Carcinogenesis in Radiosensitive Mutant Mice

放射敏感性突变小鼠 DNA 修复与癌发生的关系

基本信息

批准号：
07670263
负责人：
OGIU Toshiaki
金额：
$ 1.41万
依托单位：
National Insutitute of Radiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Severe combined immunodeficient (scid) mice are known to be radiosensitive due to their heritable defects of repair of double strand breaks induced by ionizing radiation. We studied the effects of scid mutation on the acute as well as late effects of radiation. Acute 50% lethal dose of gamma-rays for scid, Fl and C.B-17 mice was 4.1,6.5 and 7.1 Gy, respectively. When mice were irradiated with same dose, survival period of Fl mice was shorter than that of C.B-17 mice. The bone marrow cells of scid mice were also radiosensitive as compared to those from other 2 strains. Bone marrow cells from Fl mice were slightly but significantly more radiosensitive than that from C.B-17 mice. These results mean that scid hetrozygotes are more resistant to ionizing radiation when compared with scid homozygotes, but more sensitive than wild-type. In late effect studies, groups of scid, Fl and C.B-17 mice were exposed to a single whole body dose of 1-3 Gy of gamma-rays. Results clearly indicated that scid mice were extremely susceptible for induction of thymic lymphomas as compared to other 2 strains. No difference for induction of thymic lymphomas was observed between Fl mice and C.B-17 mice. Ethyl-nitrosourea, a strong lymphomagen, was administered to scid mice. However, incidence of thymic lymphomas were not so high. These results indicate that close relationship between radiosensitivity and susceptibility for radiogenic development of thymic lymphomas was proved, but effect of scid heterozygosity was not demonstrated. Almost all thymic lymphomas of scid mice were CD4/CD8 double positive. In other organs, relationship between radiosensitivity and susceptibility for tumor development was not demonstrated in this system. Further studies are needed to analyze the effects of scid mutation radiation-induced development of solid tumors.

严重联合免疫缺陷（scid）小鼠由于其电离辐射诱导的双链断裂修复的遗传缺陷而被认为是辐射敏感的。我们研究了scid突变对辐射的急性效应和迟发效应的影响。scid、F1和C.B-17小鼠急性半致死剂量分别为4.1、6.5和7.1戈伊。在相同剂量照射下，F1小鼠的存活期短于C.B-17小鼠。scid小鼠的骨髓细胞也比其他两个品系的骨髓细胞放射敏感。F1小鼠骨髓细胞的放射敏感性略高于C.B-17小鼠。这些结果意味着，与scid纯合子相比，scid杂合子对电离辐射的抵抗力更强，但比野生型更敏感。在晚期效应研究中，将scid、F1和C.B-17小鼠组暴露于1-3戈伊的单次全身剂量的γ射线。结果清楚地表明，scid小鼠是非常容易诱发胸腺淋巴瘤相比，其他两个品系。在F1小鼠和C.B-17小鼠之间没有观察到胸腺淋巴瘤的诱导差异。乙基亚硝基脲，一种强淋巴瘤原，被给予scid小鼠。但胸腺淋巴瘤的发病率并不高。这些结果表明，胸腺淋巴瘤的放射敏感性与放射发生的易感性密切相关，而scid杂合子的影响则不明显。几乎所有scid小鼠胸腺淋巴瘤均为CD 4/CD 8双阳性。在其他器官中，放射敏感性与肿瘤发生易感性之间的关系在该系统中未得到证实。需要进一步的研究来分析scid突变对辐射诱发实体瘤发展的影响。