Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure

Akuwudike, Pamela; López-Riego, Milagrosa; Ginter, J.; Cheng, Lei; Wieczorek, Anna; Życieńska, Katarzyna; Łysek-Gładysińska, Małgorzata; Wójcik, Andrzej; Brzozowska, B.; Lundholm, Lovisa

doi:10.1016/j.dnarep.2023.103554

DNA Repair

2023

DOI: 10.1016/j.dnarep.2023.103554

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Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure

Pamela Akuwudike

Milagrosa López-Riego

J. Ginter

et al.

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2024

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DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures

Strobel,

Schumann,

Müller

et al. 2024

IJMS

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The combination of high and low LET radionuclides has been tested in several patient studies to improve treatment response. Radionuclide mixtures can also be released in nuclear power plant accidents or nuclear bomb deployment. This study investigated the DNA damage response and DNA double-strand break (DSB) repair in peripheral blood mononuclear cells (PBMCs) after internal exposure of blood samples of 10 healthy volunteers to either no radiation (baseline) or different radionuclide mixtures of the α- and β-emitters [223Ra]RaCl2 and [177Lu]LuCl3, i.e., 25 mGy/75 mGy, 50 mGy/50 mGy and 75 mGy/25 mGy, respectively. DSB foci and γ-H2AX α-track enumeration directly after 1 h of exposure or after 4 h or 24 h of repair revealed that radiation-induced foci (RIF) and α-track induction in 100 cells was similar for mixed α/β and pure internal α- or β-irradiation, as were the repair rates for all radiation qualities. In contrast, the fraction of unrepaired RIF (Qβ) in PBMCs after mixed α/β-irradiation (50% 223Ra & 50% 177Lu: Qβ = 0.23 ± 0.10) was significantly elevated relative to pure β-irradiation (50 mGy: Qβ, pure = 0.06 ± 0.02), with a similar trend being noted for all mixtures. This α-dose-dependent increase in persistent foci likely relates to the formation of complex DNA damage that remains difficult to repair.

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DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures

Strobel,

Schumann,

Müller

et al. 2024

IJMS

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show abstract

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Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure

Cited by 1 publication

References 39 publications

DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures

DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures

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