Relationship between DNA Repair and Carcinogenesis in Radiosensitive Mutant Mice

严重联合免疫缺陷(SCID)小鼠由于其电离辐射引起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突变对辐射急性和远期效应的影响。对SCID、F1和C.B-17小鼠的急性半数致死剂量分别为4.1Gy6.5和7.1Gy.相同剂量照射后，F1小鼠的存活时间明显短于C.B-17小鼠。与其他2个品系相比，SCID小鼠的骨髓细胞也具有辐射敏感性。F1小鼠的骨髓细胞对辐射的敏感性略高于C.B-17小鼠，但显著高于C.B-17小鼠。这些结果表明，与SCID纯合子相比，SCID杂合子对电离辐射的抗性更强，但比野生型更敏感。在后期效应研究中，SCID、F1和C.B-17组小鼠被暴露于1-3Gy射线的单次全身剂量。结果表明，与其他2个品系相比，SCID小鼠极易诱发胸腺淋巴瘤。未观察到F1小鼠和C.B-17小鼠诱发胸腺淋巴瘤的差异。乙基亚硝脲是一种很强的淋巴生长因子，用来治疗SCID小鼠。然而，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易感性密切相关，但SCID杂合子的作用不明显。几乎所有SCID小鼠胸腺淋巴瘤均为CD4/CD8双阳性。在其他器官中，放射敏感性与肿瘤发展的敏感性之间的关系在该系统中没有得到证实。需要进一步的研究来分析SCID突变辐射诱导实体瘤发展的影响。

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.