Tempel K, Spath A
Arbeitsgruppe Radiologie, Tierärztlichen Fakultät, Universität München.
Strahlenther Onkol. 1988 Mar;164(3):173-80.
The inhibition of the semiconservative and restorative DNA synthesis caused by hyperthermia (30 to 60 min, 43 degrees C) was significantly higher in spleen cells than in thymus cells. The DNA repair synthesis of thymus cells measured at 37 degrees C was increased by about two times the initial value after a pre-incubation of 30 to 90 min and 30 to 60 min, respectively, with 37 and 43 degrees C, respectively. Under the same conditions, the 3H-thymidine incorporation into the DNA of spleen cells diminished proportionally to the pre-incubation time after a pre-incubation of 30 and 45 min, respectively, with 43 and 37 degrees C, respectively. When hyperthermia and inhibitors of DNA synthesis or DNA repair (hydroxyurea, 1-beta-D-arabinofuranosylcytosine, 3',5'-didesoxythymidine, and 3-aminobenzamide) were combined, overadditive effects--without cell specific particularities--were seen only in the case of 3-aminobenzamide. Only in thymus cells, the inhibitor of DNA topoisomerase II novobiocin caused an overadditive reinforcement of the inhibition induced by hyperthermia of the semiconservative DNA synthesis. The stimulation of DNA repair synthesis in thymus cells caused by novobiocin with the aid of DNA polymerase beta could be compensated by hyperthermia. The sedimentation of thymus and spleen cell nucleoids was increased after hyperthermia. The results suggest a special importance of DNA topology and of the DNA polymerase beta activity for the cellular effect of hyperthermia.
高温(43℃,30至60分钟)对脾脏细胞半保留性和修复性DNA合成的抑制作用明显高于胸腺细胞。分别在37℃和43℃预孵育30至90分钟以及30至60分钟后,37℃下测得的胸腺细胞DNA修复合成增加至初始值的约两倍。在相同条件下,分别在43℃和37℃预孵育30分钟和45分钟后,脾脏细胞DNA中3H-胸腺嘧啶核苷的掺入量与预孵育时间成比例减少。当高温与DNA合成或DNA修复抑制剂(羟基脲、1-β-D-阿拉伯呋喃糖基胞嘧啶、3',5'-双脱氧胸苷和3-氨基苯甲酰胺)联合使用时,仅在3-氨基苯甲酰胺的情况下观察到超相加效应(无细胞特异性差异)。仅在胸腺细胞中,DNA拓扑异构酶II抑制剂新生霉素导致高温对半保留性DNA合成诱导的抑制作用超相加增强。新生霉素借助DNA聚合酶β对胸腺细胞DNA修复合成的刺激作用可被高温抵消。高温后胸腺和脾脏细胞核类物质的沉降增加。结果表明DNA拓扑结构和DNA聚合酶β活性对高温的细胞效应具有特殊重要性。