Institute of Chemical Physics, Russian Academy of Sciences, 119991, Moscow, Russian Federation; Institute of Problems of Chemical Physics, Russian Academy of Sciences, 142432, Chernogolovka, Russian Federation; Scientific Center of the Russian Academy of Sciences, 142432, Chernogolovka, Russian Federation; Moscow State University, Russian Federation.
Russian National Research Medical University, Moscow, 119997, Russian Federation.
Arch Biochem Biophys. 2019 May 30;667:30-35. doi: 10.1016/j.abb.2019.04.005. Epub 2019 Apr 25.
Nuclear magnetic ions Mg, Ca, and Zn suppress DNA synthesis by 3-5 times with respect to ions with nonmagnetic nuclei. This observation unambiguously evidences that the DNA synthesis occurs by radical pair mechanism, which is well known in chemistry and implies pairwise generation of radicals by electron transfer between reaction partners. This mechanism coexists with generally accepted nucleophilic one; it is switched on, when at least two ions enter into the catalytic site. It is induced by both sorts of ions, magnetic and nonmagnetic but it functions by 3-5 times more efficiently with magnetic ions stimulating radical pair mechanism. Decreasing catalytic activity of polymerases by 3-5 times, nuclear magnetic ions Mg, Ca, and Zn even more strongly, by 30-50 times, increase mortality of cancer cells. The two reasons of this unique phenomenon are suggested: first, the high concentration of nuclear magnetic ions delivered by specific nano-container into the cancer cells, and, second, generation of short DNA fragments by polymerases loaded with nuclear magnetic ions, which is known to activate protein p53, efficiently stimulating apoptosis of cancer cells.
核磁离子 Mg、Ca 和 Zn 会使 DNA 合成抑制 3-5 倍，而相对应的非核磁离子则不会。这一观察结果明确证明了 DNA 合成是通过自由基对机制发生的，这种机制在化学中是众所周知的，意味着反应伙伴之间通过电子转移成对地产生自由基。这种机制与公认的亲核机制并存；当至少有两个离子进入催化位点时，它就会被激活。它可以被两种离子，即磁性离子和非磁性离子诱导，但在磁场离子刺激自由基对机制时，其效率会提高 3-5 倍。核磁离子 Mg、Ca 和 Zn 通过降低聚合酶的催化活性 3-5 倍，甚至更强烈地降低 30-50 倍，从而增加癌细胞的死亡率。这一独特现象有两个原因：第一，通过特定的纳米容器将高浓度的核磁离子输送到癌细胞中；第二，被核磁离子负载的聚合酶产生短的 DNA 片段，已知这会激活蛋白 p53，有效地刺激癌细胞凋亡。
