Virsik-Peuckert P, Volkmer B, Mehmel D
Institut für Medizinische Physik und Biophysik, Universität, Göttingen, Germany.
Int J Radiat Biol. 1995 Sep;68(3):235-43. doi: 10.1080/09553009514551161.
CHO K1-cells, arrested in G0/G1 phase were irradiated with graded doses of 150-kV X-rays, and the dicentric chromosome aberrations in the first metaphase after reincubation in full growth medium were evaluated. When 500 microM ara A was administered at least 1 h before irradiation, maximal enhancement of the dicentric yield was obtained under 'immediate plating' conditions as well as under 'delayed plating' conditions, and under both conditions only the linear component alpha D of the aberration yield was affected. Since ara A had no effect upon the number of induced dsbs, as measured with PFGE at doses up to 100 Gy, the action pathway of ara A is suggested to be the repair/misrepair process manifested in the linear component of the dicentric yield. By varying the time at which either ara A at 37 degrees C was administered before irradiation or ara A at 4 degrees C was added after irradiation, it was observed that the repair step sensitive to ara A was completed within about 5 min after irradiation. This is in agreement with other observations of ara A action upon a fast repair step. The conversion of DNA single-strand breaks or base damage sites into double-strand breaks as a consequence of polymerase beta inhibition by ara A would explain the present results.
将处于G0/G1期的CHO K1细胞用不同剂量的150 kV X射线进行照射,然后在完全生长培养基中再培养后,评估第一个中期的双着丝粒染色体畸变情况。当在照射前至少1小时给予500 microM阿糖腺苷时,在“立即铺板”条件和“延迟铺板”条件下均获得了双着丝粒产量的最大增强,并且在这两种条件下,仅畸变产量的线性成分αD受到影响。由于用PFGE在高达100 Gy的剂量下测量时,阿糖腺苷对诱导的双链断裂数量没有影响,因此推测阿糖腺苷的作用途径是双着丝粒产量线性成分中表现出的修复/错配过程。通过改变照射前给予37℃阿糖腺苷的时间或照射后添加4℃阿糖腺苷的时间,观察到对阿糖腺苷敏感的修复步骤在照射后约5分钟内完成。这与关于阿糖腺苷对快速修复步骤作用的其他观察结果一致。阿糖腺苷对聚合酶β的抑制导致DNA单链断裂或碱基损伤位点转化为双链断裂,这可以解释目前的结果。