Radiation damage to single stranded oligonucleotide trimers labelled with 5-iodopyrimidines

Westphal, Kinga; Skotnicki, Konrad; Bobrowski, Krzysztof; Rak, Janusz

doi:10.1039/c6ob01713d

Cited by 11 publications

(15 citation statements)

References 42 publications

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“…The larger EA of brominated pyrimidines also accounts for more efficient damage induced by hydrated electrons in the trimeric oligonucleotides, TBrdXT, labeled with BrdU or BrdC [77]. Moreover, the extent of damage, especially the formation of cytotoxic single-strand breaks induced by hydrated electrons is doubled in the trimeric oligonucleotides labeled with IdU or IdC compared to their counterparts labeled with BrdU or BrdC [78]. Our studies showed unequivocally that hydrated electrons are a negligible factor in damage to native DNA even for a ionizing radiation dose exceeded many times the doses used in radiotherapy [77].…”

Section: Working Group 2: Models Of Dna Damage and Consequencesmentioning

confidence: 99%

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

Ferreri

Golding

Jahn

et al. 2016

Free Radical Research

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The COST Action CM1201 "Biomimetic Radical Chemistry" has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 -Radical Enzymes, WG2 -Models of DNA damage and consequences, WG3 -Membrane stress, signalling and defenses, and WG4 -Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders. ARTICLE HISTORY

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Section: Working Group 2: Models Of Dna Damage and Consequencesmentioning

confidence: 99%

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

Ferreri

Golding

Jahn

et al. 2016

Free Radical Research

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“…BrdU is a highly electron-affinic molecule, prone to dissociative electron attachment leading to a reactive uracil-5-yl radical via the unstable anion [13][14][15]. The promising characteristics of the electron-induced degradation of halo uracils have been demonstrated many times [16][17][18][19][20]. Recently, several new C5-pyrimidine analogues have been proposed in the context of efficient electron-induced degradation [21,22].…”

Section: Introductionmentioning

confidence: 99%

5-(N-Trifluoromethylcarboxy)aminouracil as a Potential DNA Radiosensitizer and Its Radiochemical Conversion into N-Uracil-5-yloxamic Acid

Spisz

Kozak

Chomicz-Mańka

et al. 2020

IJMS

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Hypoxia—a hallmark of solid tumors—dramatically impairs radiotherapy, one of the most common anticancer modalities. The adverse effect of the low-oxygen state can be eliminated by the concomitant use of a hypoxic cell radiosensitizer. In the present paper, we show that 5-(N-trifluoromethylcarboxy) aminouracil (CF3CONHU) can be considered as an effective radiosensitizer of DNA damage, working under hypoxia. The title compound was synthesized in the reaction of 5-aminouracil and trifluoroacetic anhydride in trifluoroacetic acid. Then, an aqueous and deoxygenated solution of the HPLC purified compound containing tert-butanol as a hydroxyl radical scavenger was irradiated with X-rays. Radiodegradation in a 26.67 ± 0.31% yield resulted in only one major product—N-uracil-5-yloxamic acid. The mechanism that is possibly responsible for the formation of the observed radioproduct has been elucidated with the use of DFT calculations. The cytotoxic test against the PC3 prostate cancer cell line and HDFa human dermal fibroblasts confirmed the low cytotoxicity of CF3CONHU. Finally, a clonogenic assay and flow cytometric analysis of histone H2A.X phosphorylation proved the radiosensitization in vitro.

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“…In the normoxic cells, damage produced by the ● OH radicals becomes “fixed” due to reaction with oxygen, while under hypoxia, naturally occurring radioprotectors like cysteine or glutathione can restore DNA through hydrogen donation [10]. Moreover, hydrated electrons, the second most abundant product of water radiolysis, are not harmful to the natural DNA [11,12]. The situation becomes quite different when DNA is labeled with nucleosides undergoing efficient DEA.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, Sanche et al [13] demonstrated efficient formation of single strand breaks in DNA oligonucleotides labeled with BrdU, when an aqueous solutions of these biopolymers were irradiated with X-rays in the presence of a hydroxyl radical scavenger. Similarly, a radiolysis of a solution containing TXT oligonucleotides (where X stands for 5-bromo-2′-deoxyuridine (BrdU), 5-iodo-2′-deoxyuridine (IdU), 5-bromo-2′-deoxycitidine (BrdC), 5-iodo-2′-deoxycitidine (IdC), 8-bromo-2′-deoxyadenosine (BrdA), or 8-bromo-2′-deoxyguanosine (BrdG)) and t -butyl alcohol ( t -BuOH) as ● OH scavenger led to strand breaks besides other types of DNA damage [11,12].…”

Section: Introductionmentioning

confidence: 99%

Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2′-Deoxyuridines?

et al. 2019

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Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2′-deoxyuridine (ISdU) as an efficient agent, increasing the extent of tumor cell killing with ionizing radiation. To our surprise, a similar derivative of 4-thio-2’-deoxyuridine, 5-bromo-4-thio-2′-deoxyuridine (BrSdU), does not show radiosensitizing properties at all. In order to explain this remarkable difference, we carried out a radiolytic (stationary and pulse) and quantum chemical studies, which allowed the pathways to all radioproducts to be rationalized. In contrast to ISdU solutions, where radiolysis leads to 4-thio-2’-deoxyuridine and its dimer, no dissociative electron attachment (DEA) products were observed for BrSdU. This observation seems to explain the lack of radiosensitizing properties of BrSdU since the efficient formation of the uridine-5-yl radical, induced by electron attachment to the modified nucleoside, is suggested to be an indispensable attribute of radiosensitizing uridines. A larger activation barrier for DEA in BrSdU, as compared to ISdU, is probably responsible for the closure of DEA channel in the former system. Indeed, besides DEA, the XSdU anions may undergo competitive protonation, which makes the release of X− kinetically forbidden.

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Radiation damage to single stranded oligonucleotide trimers labelled with 5-iodopyrimidines

Cited by 11 publications

References 42 publications

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

5-(N-Trifluoromethylcarboxy)aminouracil as a Potential DNA Radiosensitizer and Its Radiochemical Conversion into N-Uracil-5-yloxamic Acid

Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2′-Deoxyuridines?

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