Kirsanov Kirill, Fetisov Timur, Antoshina Elena, Trukhanova Lubov, Gor'kova Tatiana, Vlasova Olga, Khitrovo Irina, Lesovaya Ekaterina, Kulbachevskaya Nataliya, Shcherbakova Tatiana, Belitsky Gennady, Yakubovskaya Marianna, Švedas Vytas, Nilov Dmitry
Blokhin Cancer Research Center, Moscow, Russia.
Peoples' Friendship University of Russia, Moscow, Russia.
Front Pharmacol. 2022 Jul 6;13:842316. doi: 10.3389/fphar.2022.842316. eCollection 2022.
7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.
7-甲基鸟嘌呤（7-MG）竞争性抑制DNA修复酶聚（ADP-核糖）聚合酶（PARP）和RNA修饰酶tRNA-鸟嘌呤转糖基酶（TGT），是一种潜在的抗癌药物候选物。此外，作为一种天然化合物，它可以避免已获批的合成PARP抑制剂所具有的严重副作用。在此，我们对7-MG的毒理学和致癌特性进行了全面研究。结果表明，7-MG不会诱导突变或染色体结构异常，也没有致瘤活性。已在小鼠中确定了7-MG的治疗方案（口服50 mg/kg，每周3次），未产生不良反应或形态变化。在可移植肿瘤模型上获得的关于7-MG抗癌活性的初步数据支持了我们的结论，即7-MG有望成为化疗的新成分。
