Carubelli R, Schneider J E, Pye Q N, Floyd R A
Oklahoma Medical Research Foundation, Dean A McGee Eye Institute, Oklahoma City, USA.
Free Radic Biol Med. 1995 Feb;18(2):265-9. doi: 10.1016/0891-5849(94)e0134-5.
Incubation of the RNA phage Q beta at 37 degrees C with a mixture of 100 mM ribose and 10 microM CuSO4 resulted in a complete loss of viable phage after 20 min. This cytotoxic effect required both ribose and cupric ions. There was a direct correlation between the decrease in the percentage of phage survival and: (a) the length of incubation, and (b) the concentrations of both ribose and CuSO4. Addition of the strong chelator diethylenetriaminepentaacetic acid abolished the cytotoxic effect. These results are consistent with an initial production of superoxide free radicals by transition metal catalyzed autoxidation of ribose and Amadori products, followed by dismutation of superoxide to hydrogen peroxide and generation of lethal hydroxyl radicals by the Fenton reaction. RNA isolated from phage incubated with ribose and CuSO4 retained its infectivity, suggesting that the cytotoxic effect may be mediated by a free radical attack on proteinaceous components of the phage through a site specific generation of hydroxyl radicals on protein-bound transition metal ions.
将RNA噬菌体Qβ在37℃下与100 mM核糖和10 μM硫酸铜的混合物一起孵育，20分钟后活噬菌体完全丧失。这种细胞毒性作用需要核糖和铜离子两者。噬菌体存活率百分比的降低与以下两者之间存在直接相关性：(a)孵育时间，以及(b)核糖和硫酸铜的浓度。添加强螯合剂二乙烯三胺五乙酸消除了细胞毒性作用。这些结果与过渡金属催化核糖和阿马多里产物的自氧化最初产生超氧自由基，随后超氧歧化为过氧化氢以及通过芬顿反应产生致死性羟基自由基一致。从与核糖和硫酸铜一起孵育的噬菌体中分离出的RNA保留了其感染性，这表明细胞毒性作用可能是通过蛋白质结合的过渡金属离子上的位点特异性羟基自由基生成，对噬菌体的蛋白质成分进行自由基攻击介导的。
