Stratford M R, Clarke E D, Hodgkiss R J, Middleton R W, Wardman P
Int J Radiat Oncol Biol Phys. 1984 Aug;10(8):1353-6. doi: 10.1016/0360-3016(84)90347-x.
Nitroakridin 3582 (NA) and a nitronaphthalimide (DM113), which fluoresce only upon reduction, have been studied by HPLC. V79-379A cells incubated with NA under 20% or 2% O2 and N2 gave increasing amounts of the fluorescent amine with an hypoxic:oxic differential of 160. Measurement of the uptake of NA showed that it was concentrated within the cell by over 1000-fold. Studies in 3 different cell lines of reduction under hypoxia showed a 7-fold range in amine production. DM113 yields more than one fluorescent product, which show different absorption and fluorescence spectra. Chemical reduction of NA or DM113 using a variety of methods gave, depending on conditions, amine and/or (what was presumed to be) hydroxylamine; the latter was non-fluorescent. In vivo, NA is toxic at greater than 0.19 mumol g-1. At this dose much of the drug is found in the liver and kidneys. Plasma levels at 30 minutes are only 2 microM while tumor concentrations are 10 microM compared to 600 microM in the liver. However, the half life is greater than 1 hr and amine was detectable in these tumors.
已通过高效液相色谱法（HPLC）对仅在还原时才发出荧光的硝基吖啶3582（NA）和一种硝基萘酰亚胺（DM113）进行了研究。在20%氧气或2%氧气与氮气环境下用NA孵育的V79 - 379A细胞产生的荧光胺量不断增加，缺氧与有氧条件下的差异为160。对NA摄取的测量表明，它在细胞内的浓缩倍数超过1000倍。对3种不同细胞系在缺氧条件下还原情况的研究表明，胺生成量的范围为7倍。DM113产生不止一种荧光产物，这些产物具有不同的吸收光谱和荧光光谱。使用多种方法对NA或DM113进行化学还原，根据条件不同，会生成胺和/或（推测为）羟胺；后者无荧光。在体内，NA的毒性大于0.19 μmol g-1。在此剂量下，大部分药物存在于肝脏和肾脏中。30分钟时的血浆浓度仅为2 μM，而肿瘤浓度为10 μM，相比之下肝脏中的浓度为600 μM。然而，半衰期大于1小时，并且在这些肿瘤中可检测到胺。
