He S Q, Li C F, Zhen X Y, Zhou J, Liu T F
Department of Radiation Oncology, Cancer Hospital, Shanghai Medical University, China.
Int J Radiat Oncol Biol Phys. 1989 Feb;16(2):361-8.
Tumor cells (SGC-7901) obtained from a human gastric adenocarcinoma have been examined with regard to their intrinsic sensitivity to gamma-irradiation and as to how this intrinsic sensitivity might be altered by growth in a synthesized agent AT-1727 (N4-morpholino-methyl-3,5-dioxopiperazynyl-1,2 ethanl). Clonogenic survival was measured via colony formation assays and fitted to single-hit-multitarget formula. Exponentially growing cells exhibited the mean of survival parameters: D0 = 0.86 + 0.04 Gy; n = 7.03 + 2.3; Dq = 1.63 + 0.23 Gy and SF2 (surviving fraction of conventional daily clinical dose of 2 Gy) = 45-50%. Split-dose survival assays and delayed plating methods were used to exploit the capacity of sublethal damage repair of this cell line studied demonstrating the reappearance of initial shoulder on the survival curve and an increased survival. Alteration of radiosensitivity of SGC cells by AT-1727 was shown when cultures were incubated in a medium with the drug for a 6 hr interval between split dose irradiation, indicating the inhibition of sublethal damage repair. The radioresistance of hypoxic SGC cells was decreased when pre-treatment with AT-1727 was given 2 hr before irradiation, and the decrease of surviving fraction was drug-dose dependent. A maximum enhanced effect was obtained when 0.15 mM of AT-1727 was used, reaching an ER of 1.24. Inhibition of sublethal damage repair and action as a hypoxic radiosensitizer were considered to be two parts of the mechanism of AT-1727 in modification of radiation effects.
对源自人胃腺癌的肿瘤细胞（SGC - 7901）进行了研究，观察其对γ射线的内在敏感性，以及在合成剂AT - 1727（N4 - 吗啉代甲基 - 3,5 - 二氧代哌嗪基 - 1,2 - 乙烷）中生长时这种内在敏感性可能如何改变。通过集落形成试验测量克隆形成存活率，并将其拟合到单击多靶公式。指数生长的细胞呈现出存活参数的平均值：D0 = 0.86 ± 0.04 Gy；n = 7.03 ± 2.3；Dq = 1.63 ± 0.23 Gy，以及SF2（常规每日临床剂量2 Gy时的存活分数）= 45 - 50%。采用分次剂量存活试验和延迟接种方法来研究该细胞系的亚致死损伤修复能力，结果表明存活曲线上初始肩部再现且存活率增加。当在分次剂量照射之间将培养物在含有该药物的培养基中孵育6小时时，显示出AT - 1727对SGC细胞放射敏感性的改变，这表明亚致死损伤修复受到抑制。当在照射前2小时用AT - 1727进行预处理时，缺氧SGC细胞的放射抗性降低，且存活分数的降低呈药物剂量依赖性。当使用0.15 mM的AT - 1727时获得最大增强效果，增强比达到1.24。亚致死损伤修复的抑制和作为缺氧放射增敏剂的作用被认为是AT - 1727改变辐射效应机制的两个部分。
