Johnston P J, Bryant P E
School of Biological and Medical Sciences, University of St Andrews, Fife, U.K.
Biochem Pharmacol. 1993 Feb 9;45(3):569-72. doi: 10.1016/0006-2952(93)90128-j.
We have examined chromosome damage caused by a wide range of bleomycin (BLM) concentrations in Chinese hamster ovary (CHO-K1) cells reversibly porated by the bacterial cytotoxin streptolysin-O (SLO). Chromosome damage was measured using the micronucleus cytokinesis block technique (employing cytochalasin-B). Treatment of exponentially growing cells with 0.045 IU/mL SLO for 5 min resulted in up to a thousand-fold and a million-fold increase in biological effectiveness, compared to treatment in the absence of SLO for 24 hr and 5 min, respectively. Increases in micronuclei of 4-5 times background level were observed after only 5 min exposure to the drug in the presence of SLO at doses as low as 100 pg/mL (approximately 70 pmol/L). These results indicate that the use of SLO may facilitate the treatment of cells with BLM for periods of time resembling acute exposure to ionizing radiations.
我们检测了在中国仓鼠卵巢(CHO-K1)细胞中,由多种博来霉素(BLM)浓度导致的染色体损伤情况,这些细胞通过细菌细胞毒素链球菌溶血素-O(SLO)进行可逆性穿孔。使用微核胞质分裂阻断技术(采用细胞松弛素-B)来测量染色体损伤。与分别在无SLO的情况下处理24小时和5分钟相比,用0.045 IU/mL SLO处理指数生长期细胞5分钟,生物有效性分别提高了多达一千倍和一百万倍。在存在SLO的情况下,仅在5分钟内暴露于低至100 pg/mL(约70 pmol/L)剂量的药物后,就观察到微核增加至背景水平的4 - 5倍。这些结果表明,使用SLO可能有助于在类似于急性暴露于电离辐射的时间段内用BLM处理细胞。