Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Redox-Active Cerium Fluoride Nanoparticles Mitigate of Double-Stranded DNA Breakage and Modulate Gene Expression Due to Radiation Exposure In Vitro

Version 1 : Received: 5 December 2023 / Approved: 7 December 2023 / Online: 7 December 2023 (16:53:40 CET)

A peer-reviewed article of this Preprint also exists.

Chukavin, N.N.; Filippova, K.O.; Ermakov, A.M.; Karmanova, E.E.; Popova, N.R.; Anikina, V.A.; Ivanova, O.S.; Ivanov, V.K.; Popov, A.L. Redox-Active Cerium Fluoride Nanoparticles Selectively Modulate Cellular Response against X-ray Irradiation In Vitro. Biomedicines 2024, 12, 11. Chukavin, N.N.; Filippova, K.O.; Ermakov, A.M.; Karmanova, E.E.; Popova, N.R.; Anikina, V.A.; Ivanova, O.S.; Ivanov, V.K.; Popov, A.L. Redox-Active Cerium Fluoride Nanoparticles Selectively Modulate Cellular Response against X-ray Irradiation In Vitro. Biomedicines 2024, 12, 11.

Abstract

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells, due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells – hMSCs) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSCs from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in normal cells, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 hours after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA repair system after X ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of normal cells from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

Keywords

cerium fluoride nanoparticles; DNA reparation; double-strand brakes; X-ray radiation

Subject

Biology and Life Sciences, Life Sciences

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