Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo.
Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo.
复制标题
稠合吡嗪一氮氧化物作为生物还原药物。
DOI：
10.1097/00001813-199504000-00010
复制
发表时间：
1995
影响因子：
2.3
通讯作者：
Stratford,IJ
中科院分区：
文献类型：
--
作者：
Naylor,MA;Adams,GE;Haigh,A;Cole,S;Jenner,T;Robertson,N;Siemann,D;Stephens,MA;Stratford,IJ
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哺乳动物细胞显示出明显更大的毒性。在这些条件下产生相同水平的细胞杀伤所需的浓度差异范围从人细支气管肺泡肿瘤细胞系中的3.5到DNA链断裂修复缺陷的啮齿动物细胞系中的120。通过碱性蔗糖梯度和脉冲场凝胶电泳技术证实RB 90740在缺氧条件下引起DNA链断裂的能力。尽管这些特性在体外得到证实，但RB 90740在体内实验鼠肿瘤中对缺氧细胞没有细胞毒性。这可能部分是由于体外产生毒性所需的缺氧水平（< 0.02% O2）。
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% O 2) necessary to produce toxicity in vitro..