Naylor M A, Adams G E, Haigh A, Cole S, Jenner T, Robertson N, Siemann D, Stephens M A, Stratford I J
Experimental Oncology Division, MRC Radiobiology Unit, Chilton, Didcot, UK.
Anticancer Drugs. 1995 Apr;6(2):259-69. doi: 10.1097/00001813-199504000-00010.
RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions ranges from 3.5 in a human bronchio-alveolar tumor cell line up to 120 in a rodent cell line defective in the repair of DNA strand breaks. The ability of RB 90740 to cause DNA strand breaks under hypoxic conditions was confirmed by alkaline sucrose gradient and pulsed field gel electrophoresis techniques. Despite these properties demonstrated in vitro, RB 90740 was shown not to be cytotoxic to hypoxic cells in experimental murine tumors in vivo. This may be due, in part, to the level of hypoxia (< 0.02% O2) necessary to produce toxicity in vitro.
RB 90740是一系列芳香族单N -氧化物生物还原药物中的先导化合物。该化合物在体外对缺氧的哺乳动物细胞比对有氧的哺乳动物细胞表现出更大的毒性。在这些条件下，产生相同程度细胞杀伤所需浓度的差异范围，在人支气管肺泡肿瘤细胞系中为3.5倍，在DNA链断裂修复有缺陷的啮齿动物细胞系中高达120倍。通过碱性蔗糖梯度和脉冲场凝胶电泳技术证实了RB 90740在缺氧条件下导致DNA链断裂的能力。尽管在体外表现出这些特性，但RB 90740在实验性小鼠肿瘤体内对缺氧细胞没有细胞毒性。这可能部分归因于在体外产生毒性所需的缺氧水平（<0.02% O2）。
