Consequences of Electron Attachment to Modified Nucleosides Incorporated into DNA

Chomicz-Mańka, Lidia; Wityk, Paweł; Golon, Łukasz; Zdrowowicz, Magdalena; Wiczk, Justyna; Westphal, Kinga; Żyndul, Michał; Makurat, Samanta; Rak, Janusz

doi:10.1007/978-3-319-27282-5_48

Cited by 1 publication

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“…Due to the fact that the number of radiosensitizers employed in clinics is surprisingly small, it seems rational to look for and test new potentially radiosensitizing molecules. One of the widely studied groups of sensitizers are uracil analogues such as 5-bromo-2 -deoxyuridine (BrdU) [7,8]. Their sensitization mechanism is likely related to the rapid reaction of the modified nucleobase with hydrated electrons which are one of the main products of the water radiolysis [9] that takes place during the exposure of cells to ionizing radiation and which are not utilized by classical RT.…”

Section: Introductionmentioning

confidence: 99%

Radiosensitization of PC3 Prostate Cancer Cells by 5-Thiocyanato-2′-deoxyuridine

Zdrowowicz

Datta

Rychłowski

et al. 2022

Cancers

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Purpose: The radiosensitizing properties of uracil analogs modified in the C5 position are very interesting in the context of their effectiveness and safety in radiation therapy. Recently, radiation chemical studies have confirmed that 5-thiocyanato-2′-deoxyuridine (SCNdU) undergoes dissociation induced by an excess electron attachment and established this nucleoside as a potential radiosensitizer. In this paper, we verify the sensitizing properties of SCNdU at the cellular level and prove that it can effectively enhance ionizing radiation-induced cellular death. Methods and Materials: Prostate cancer cells were treated with SCNdU and irradiated with X rays. The cytotoxicity of SCNdU was determined by MTT test. Cell proliferation was assessed using a clonogenic assay. Cell cycle analyses, DNA damage, and cell death analyses were performed by flow cytometry. Results: SCNdU treatment significantly suppressed the proliferation and increased the radiosensitivity of prostate cancer cells. The radiosensitizing effect expressed by the dose enhancement factor is equal to 1.69. Simultaneous exposure of cells to SCNdU and radiation causes an increase in the fraction of the most radiosensitive G2/M phase, enhancement of the histone H2A.X phosphorylation level, and apoptosis induction. Finally, SCNdU turned out to be marginally cytotoxic in the absence of ionizing radiation. Conclusions: Our findings indicate that SCNdU treatment enhances the radiosensitivity of prostate cancer cells in a manner associated with the cell cycle regulation, double strand formation, and a slight induction of apoptosis.

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Section: Introductionmentioning

confidence: 99%