| Autor: |
Proskurnina EV; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Mikheev IV; Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow 119991, Russia., Savinova EA; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Ershova ES; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Veiko NN; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Kameneva LV; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Dolgikh OA; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Rodionov IV; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia., Proskurnin MA; Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow 119991, Russia., Kostyuk SV; Laboratory of Molecular Biology, Research Centre for Medical Genetics, 1 Moskvorechye St, Moscow 115522, Russia. |
| Abstrakt: |
Fullerenes and metallofullerenes play an active role in homeostasis of reactive oxygen species and may cause oxidative damage to cells. As pristine fullerenes are a basis for derivatization, studying oxidative DNA damage/repair and apoptosis is important in terms of genotoxicity and cytotoxicity for their biomedical application. Aqueous dispersions of C 60 , C 70 , and Gd@C 82 (5 nM and 1.5 μM) were cultured with human fetal lung fibroblasts for 1, 3, 24, and 72 h. Oxidative DNA damage/repair was assessed through concentration of 8-oxodG, double-strand breaks, and activation of BRCA1. Activity of apoptosis was assessed through the BCL2/BAX ratio. All three fullerenes caused oxidative modification of DNA at the early stages; C 60 caused the most long-term damage, Gd@C 82 caused the most short-term damage, and C 70 caused "wave-like" dynamics. The dynamics of DNA repair correlated with the dynamics of oxidative damage, but Gd@C 82 caused more prolonged activation of the repair system than C 60 or C 70 . The oxidative toxicity of Gd@C 82 , is minor and the oxidative toxicity of C 60 is mild and short-term, in contrast to C 70 . In relation to the studied effects, the fullerenes can be arranged in a safety row of Gd@C 82 > C 60 > C 70 . |
