Stryker J A, Gerweck L E
Edwin L. Steele Laboratory, Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Radiat Res. 1988 Feb;113(2):356-61.
The inhibitory effect of lonidamine 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid on oxygen utilization by Chinese hamster ovary (CHO) and murine fibrosarcoma (FSa-II) cells was evaluated with a Clark oxygen electrode. The drug produced a small but statistically significant inhibition of oxygen uptake at normal pH (7.4) in CHO and FSa-II cells of 16 and 11%, respectively. However, at low pH (6.65) the inhibitory effect of lonidamine increased dramatically to 60% in both CHO and FSa-II cells. Because of the potential difference between tumor and normal tissue pH, lonidamine and similar drugs may be effective for selectively modifying oxygen utilization and concentration in tumor tissue which might lead to increased radiation and hyperthermic sensitization in tumors compared to normal tissue, resulting in an improvement in the therapeutic ratio.
用克拉克氧电极评估了氯尼达明（1-(2,4-二氯苄基)-1H-吲唑-3-羧酸）对中国仓鼠卵巢（CHO）细胞和小鼠纤维肉瘤（FSa-II）细胞氧利用的抑制作用。在正常pH值（7.4）下，该药物对CHO细胞和FSa-II细胞的氧摄取产生了轻微但具有统计学意义的抑制，分别为16%和11%。然而，在低pH值（6.65）时，氯尼达明在CHO细胞和FSa-II细胞中的抑制作用均显著增加至60%。由于肿瘤组织和正常组织pH值存在差异，氯尼达明及类似药物可能有效地选择性改变肿瘤组织中的氧利用和浓度，这可能导致肿瘤组织相对于正常组织对辐射和热疗的敏感性增加，从而提高治疗比率。
