Abdullaev Serazhutdin, Minkabirova Gulchachak, Karmanova Ekaterina, Bruskov Vadim, Gaziev Azhub
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russian Federation.
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russian Federation; Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region, 142290, Russian Federation.
Mutat Res Genet Toxicol Environ Mutagen. 2018 Jul;831:13-18. doi: 10.1016/j.mrgentox.2018.05.006. Epub 2018 May 5.
An antidiabetic drug metformin has anticarcinogenic and geroprotective effects and has been used in combination with radiation cancer therapy. The present work is devoted to the study of the effect of metformin on survival in mice, the frequency of micronuclei in mouse bone marrow cells and excretion of cell-free nuclear and mitochondrial DNA in the urine of X-ray-exposed rats. The survival rate and the frequency of micronuclei in mice and excretion of DNA into rat urine were determined after administration of the drug before and after irradiation of animals. The DNA content was measured by qRT-PCR. Metformin shows a radioprotective effect only when administered to mice after the radiation exposure. On the 11th day after irradiation, we observed 100% mortality in the control group; 78% of mice remained alive if metformin was given. Twenty percent of the mice in this group survived for 30 days after irradiation. Metformin has the same effect on the frequency of micronuclei; its reduction is observed, when the drug is administered to the mice after irradiation. Metformin promotes the excretion of nuclear and mitochondrial DNA with the urine of irradiated rats. The results show that metformin acts as a radiomitigation effector. Metformin promotes the active excretion of DNA of dying cells from the tissues of irradiated animals.
一种抗糖尿病药物二甲双胍具有抗癌和保护衰老的作用，并已与放射癌症治疗联合使用。目前的工作致力于研究二甲双胍对小鼠存活率、小鼠骨髓细胞微核频率以及受X射线照射大鼠尿液中游离细胞核和线粒体DNA排泄的影响。在动物照射前后给药后，测定小鼠的存活率和微核频率以及DNA向大鼠尿液中的排泄情况。通过qRT-PCR测量DNA含量。二甲双胍仅在辐射暴露后给小鼠给药时才显示出辐射保护作用。照射后第11天，我们观察到对照组死亡率为100%；如果给予二甲双胍，78%的小鼠存活。该组中20%的小鼠在照射后存活了30天。二甲双胍对微核频率有相同的影响；当在照射后给小鼠给药时，观察到微核频率降低。二甲双胍促进受照射大鼠尿液中细胞核和线粒体DNA的排泄。结果表明，二甲双胍起到辐射缓解效应器的作用。二甲双胍促进死亡细胞的DNA从受照射动物组织中主动排泄。
