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

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Effects of Aqueous Dispersions of C60, C70, and Gd@C82 Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblasts
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-02-23 , DOI: 10.1021/acsbiomaterials.2c01359
Elena V Proskurnina ₁ , Ivan V Mikheev ₂ , Ekaterina A Savinova ₁ , Elizaveta S Ershova ₁ , Natalia N Veiko ₁ , Larisa V Kameneva ₁ , Olga A Dolgikh ₁ , Ivan V Rodionov ₁ , Mikhail A Proskurnin ₂ , Svetlana V Kostyuk ₁

Affiliation

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.

中文翻译：

C60、C70 和 Gd@C82 富勒烯水分散体对人胚胎肺成纤维细胞 DNA 氧化损伤/修复和凋亡的影响

富勒烯和金属富勒烯在活性氧的稳态中发挥积极作用，并可能对细胞造成氧化损伤。由于原始富勒烯是衍生化的基础，因此研究氧化 DNA 损伤/修复和细胞凋亡在其生物医学应用的遗传毒性和细胞毒性方面具有重要意义。_{C 60}、C ₇₀和Gd@C ₈₂ （5 nM 和1.5 μM）的水分散体与人胎儿肺成纤维细胞一起培养1、3、24和72小时。通过 8-oxodG 的浓度、双链断裂和 BRCA1 的激活来评估氧化 DNA 损伤/修复。通过 BCL2/BAX 比率评估细胞凋亡的活性。所有三种富勒烯都会在早期阶段引起 DNA 的氧化修饰；C ₆₀造成最长期的损害，Gd@C ₈₂造成最短期的损害，而 C ₇₀造成“波状”动力学。DNA 修复的动力学与氧化损伤的动力学相关，但与 C ₆₀或 C _{70相比，Gd@C}₈₂导致修复系统的激活时间更长。_{Gd@C 82}的氧化毒性较小，与 C _70相比，C₆₀的氧化毒性温和且短期。关于所研究的效果，富勒烯可以排列在 Gd@C ₈₂ > C ₆₀ > C ₇₀的安全行中。

更新日期：2023-02-23

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