Effects of Aqueous Dispersions of C₆₀, C₇₀, and Gd@C₈₂ Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblasts

Abstract

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 .