Ludwig C U, Bowden G T, Roberts R A, Alberts D S
Cancer Treat Rep. 1984 Feb;68(2):367-72.
The effect of hypoxia on bisantrene-induced cytotoxicity and protein-associated DNA strand breaks was studied in mouse L1210 leukemia cells, human T47D breast cancer cell line, and fresh samples of human tumor cells. For each cell type, there was enhanced cell killing under oxic versus hypoxic conditions (1-hour drug treatment at 37 degrees C). Likewise, in L1210 cells, the frequency of bisantrene (10 micrograms/ml for 1 hour)-induced protein-associated DNA strand breaks was reduced by 70% under hypoxic versus oxic conditions. The reason for enhanced cytotoxicity and DNA strand breakage in L1210 cells under oxic conditions could not be attributed to oxygen-enhanced cellular uptake of the drug. The clinical implication of these data is that bisantrene may be relatively ineffective against large tumors containing hypoxic cell populations.
在小鼠L1210白血病细胞、人T47D乳腺癌细胞系以及新鲜的人肿瘤细胞样本中，研究了缺氧对双胺苯吖啶诱导的细胞毒性和蛋白质相关DNA链断裂的影响。对于每种细胞类型，在有氧与缺氧条件下（37℃进行1小时药物处理），细胞杀伤作用均增强。同样，在L1210细胞中，与有氧条件相比，缺氧条件下双胺苯吖啶（10微克/毫升，处理1小时）诱导的蛋白质相关DNA链断裂频率降低了70%。L1210细胞在有氧条件下细胞毒性和DNA链断裂增强的原因不能归因于氧气增强了药物的细胞摄取。这些数据的临床意义在于，双胺苯吖啶可能对含有缺氧细胞群体的大肿瘤相对无效。
