Possible repair of carcinogenic damage caused by dimethylnitrosamine in rat kidney
Possible repair of carcinogenic damage caused by dimethylnitrosamine in rat kidney
复制标题
二甲基亚硝胺引起的大鼠肾脏致癌损伤的可能修复
作者：
P. Swann;P. Magee;U. Mohr;G. Reznik;U. Green;D. Kaufman
自从发现色素性干皮病（一种与癌症高发相关的疾病）患者的细胞可能无法从 DNA1 中切除紫外线诱导的胸腺嘧啶二聚体，并认识到所有致癌物都可能与诱发肿瘤的器官的 DNA 发生反应2 以来，人们认为修复致癌物在 DNA 中产生的变化可能对于调节这些化合物的有效性很重要。然而，对长期服用各种化学物质3的致癌作用的研究表明，单个致癌剂量的作用完全是累积的，并且致癌损害是永久性的且无法修复4。如果这是正确的，那么致癌物对 DNA 损伤的修复似乎与致癌没有直接关系。 Elkind 和 Sutton5 的经典实验建立了从辐射致死效应中恢复的方法，其中培养的细胞在第一次和第二次剂量之间以不同的间隔照射两次；如果第一剂和第二剂之间经过足够的时间，则剂量的效果不会累积。我们使用类似的实验设计来研究二甲基亚硝胺在诱导大鼠肾肿瘤中的累积效应。实验尚未完成，但我们相信我们已经证明了修复过程的存在。
SINCE the discovery that cells from patients with xeroderma pigmentosum, a disease associated with a high incidence of cancer, may be unable to excise ultraviolet light-induced thymine dimers from DNA1, and the recognition of the possibility that all carcinogens react with the DNA of the organs in which tumours are induced2, it has been thought that repair of changes produced in DNA by carcinogens might be important in moderating the effectiveness of these compounds. Work on the carcinogenic effect of prolonged administration of various chemicals3, however, suggests that individual carcinogenic doses are entirely cumulative in their action, and that the carcinogenic damage is permanent and not repaired4. If this were correct, repair of lesions produced in DNA by carcinogens would seem to have no direct relevance to carcinogenesis. Recovery from the lethal effects of radiation was established by the classic experiments of Elkind and Sutton5 in which cultured cells were irradiated twice with different intervals between the first and second dose; if sufficient time elapsed between the first and second dose, the effects of the doses were not cumulative. We have used an analogous experimental design to study the cumulation of the effect of dimethylnitrosamine in the induction of kidney tumours in the rat. The experiment is not yet complete, but we believe we have demonstrated that a repair process exists.