Effects of Aqueous Dispersions of C60, C70, and Gd@C82 Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblastsстатья
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Аннотация: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 C60, C70, and Gd@C82 (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; C60 caused the most long-term damage, Gd@C82 caused the most short-term damage, and C70 caused “wave-like” dynamics. The dynamics of DNA repair correlated with the dynamics of oxidative damage, but Gd@C82 caused more prolonged activation of the repair system than C60 or C70. The oxidative toxicity of Gd@C82, is minor and the oxidative toxicity of C60 is mild and short-term, in contrast to C70. In relation to the studied effects, the fullerenes can be arranged in a safety row of Gd@C82 > C60 > C70.
