Article Dans Une Revue J.Phys.Chem.Lett. Année : 2025

Electron-Induced Fragmentation of 5-Iodouridine: Implications for Enhanced Radiotherapy

Résumé

5-Iodouridine is a known and potentially efficient radiosensitizer; however, it has not been considered for clinical use because of its poor metabolic incorporation into DNA. Recent development of a novel pro-drug, ropidoxuridine, has improved the bioavailability of this halogenated nucleoside, although the exact mechanism of its radiosensitizing action remains not fully elucidated. Here, we demonstrate that low-energy electrons─abundantly generated along radiation tracks─efficiently dissociate the halogenated nucleoside via the primary pathway (99%), producing an iodine anion and a uridine-yl• neutral radical, with a high approximate DEA cross section of (2.7 ± 1.9)×10–14 cm2. The latter, known to be highly reactive, subsequently induces hydrogen abstraction, leading to DNA strand breaks. The damage induced in 5IUrd by low-energy electrons is found to be about 700 times greater than that in thymidine and about 4 times that of the clinically used 5-fluorouridine. These findings may contribute to the development of future cancer therapy strategies by synergistically combining 5IUrd with cisplatin or gold nanoparticles, which act as a source of secondary low-energy electrons during radiation therapy.

Dates et versions

hal-05325526 , version 1 (22-10-2025)

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Citer

Janina Kopyra, Paulina Wierzbicka, Hassan Abdoul-Carime. Electron-Induced Fragmentation of 5-Iodouridine: Implications for Enhanced Radiotherapy. J.Phys.Chem.Lett., 2025, 16 (41), pp.10536-10541. ⟨10.1021/acs.jpclett.5c01615⟩. ⟨hal-05325526⟩
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