Simultaneous alteration ofde novoandsalvagepathway to the deoxynucleoside triphosphate pool by (E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) and zidovudine (AZT) results in increased radiosensitivityin vitro

Coucke, Philippe; Cottin, E; Décosterd, Laurent A.

doi:10.1080/02841860601137389

Cited by 11 publications

(11 citation statements)

References 31 publications

(19 reference statements)

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“…As a result, the dNTP synthesis pathway is the predominant mechanism for supplying dNTPs in the brain. 71,72 The DNA repair pathway for removal of an incorrect DNA base, such as one of the most abundant alcohol-induced DNA base lesions oxo8dG, is BER. 73 Acetaldehyde-derived cross-links are repaired by the FA-linked pathway, coordinated with classical NER, applicable to non-replicating cells such as neurons.…”

Section: Alcohol and Ocmmentioning

confidence: 99%

DNA damage and neurotoxicity of chronic alcohol abuse

Kruman

Henderson

Bergeson

2012

Exp Biol Med (Maywood)

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Chronic alcohol abuse results in a variety of pathological effects including damage to the brain. The causes of alcohol-induced brain pathology are presently unclear. Several mechanisms of pathogenicity of chronic alcoholism have been proposed, including accumulation of DNA damage in the absence of repair, resulting in genomic instability and death of neurons. Genomic instability is a unified genetic mechanism leading to a variety of neurodegenerative disorders. Ethanol also likely interacts with various metabolic pathways, including one-carbon metabolism (OCM). OCM is critical for the synthesis of DNA precursors, essential for DNA repair, and as a methyl donor for various methylation events, including DNA methylation. Both DNA repair and DNA methylation are critical for maintaining genomic stability. In this review, we outline the role of DNA damage and DNA repair dysfunction in chronic alcohol-induced neurodegeneration.

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Section: Alcohol and Ocmmentioning

confidence: 99%

DNA damage and neurotoxicity of chronic alcohol abuse

Kruman

Henderson

Bergeson

2012

Exp Biol Med (Maywood)

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“…Also, in irradiated human colon cancer cells,4 in irradiated human larynx squamous carcinoma cells,5 and in irradiated human malignant glioma cells6, 3′-AZT has been shown to be a significant radiosensitizer. Furthermore, it has been reported that 3′-AZT substantially enhances γ-irradiation killing of EBV (Epstein-Barr virus)-transformed lymphoblastoid cells in vitro 7…”

Section: Introductionmentioning

confidence: 99%

Formation of Aminyl Radicals on Electron Attachment to AZT: Abstraction from the Sugar Phosphate Backbone versus One-Electron Oxidation of Guanine

et al. 2010

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Employing electron spin resonance (ESR) spectroscopy, we have characterized the radicals formed in 3′-Azido-3′-deoxythymidine (3′-AZT) and in its 5′-analog 5′-azido-5′-deoxythymidine (5′-AZT) after electron attachment in γ-irradiated aqueous (H 2 O or D 2 O) glassy (7.5 M LiCl) systems. ESR spectral studies and theoretical calculations show that the predominant site of electron capture in 3′-AZT and in 5′-AZT is at the azide group and not at the thymine moiety. The azide group in AZT is therefore more electron affinic than the most electron affinic DNA base, thymine. Electron attachment to 3′-AZT and 5′-AZT results in an unstable azide anion radical intermediate (RN 3 • − ) that is too short lived to be observed in our work even at 77 K. At 77 K we observe the neutral aminyl radical (RNH•) after loss of N 2 from RN 3 • − followed by protonation of nitrene anion radical (RN• − ) to give RNH•. The expected RN• − intermediate is not observed as protonation from water is complete at 77 K even in under highly basic conditions. Formation of RND• in D 2 O solutions confirms water as the source of the NH proton in the RNH•. Our assignments to these radicals are aided by DFT calculations for hyperfine coupling constants which closely match the experimental values. On annealing to higher temperatures (ca. 160-170 K), RNH• undergoes bimolecular hydrogen abstraction reactions from the thymine methyl group and the sugar moiety resulting in the formation of the thymine allyl radical (UCH 2 •) and two sugar radicals -C3′•, C5′•. RNH• also results in one-electron oxidation of the guanine base in 3′-AZG. This work provides a potential mechanism for the reported radiosensitization effects of AZT.

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“…A direct correlation between cell death and micronuclei-induction was obtained in HeLa cells exposed at increasing doses of γ-irradiation in the presence of an aqueous solution (0.1 µM) of 3′-AZT [129]. Moreover, 3′-AZT causes significant radiosensitization in irradiated human colon cancer cells [130], in irradiated human larynx squamous carcinoma cells [131], and in irradiated human malignant glioma cells [132]. 3′-AZT substantially enhanced γ-irradiation killing of EBV (Epstein-Barr virus)-transformed lymphoblastoid cells in vitro [133].…”

Section: C5-modified Pyrimidine Nucleosides As Radiosensitizers (Rmentioning

confidence: 99%

Reaction of Electrons with DNA: Radiation Damage to Radiosensitization

Kumar

Becker

Adhikary

et al. 2019

IJMS

117

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This review article provides a concise overview of electron involvement in DNA radiation damage. The review begins with the various states of radiation-produced electrons: Secondary electrons (SE), low energy electrons (LEE), electrons at near zero kinetic energy in water (quasi-free electrons, (e−qf)) electrons in the process of solvation in water (presolvated electrons, e−pre), and fully solvated electrons (e−aq). A current summary of the structure of e−aq, and its reactions with DNA-model systems is presented. Theoretical works on reduction potentials of DNA-bases were found to be in agreement with experiments. This review points out the proposed role of LEE-induced frank DNA-strand breaks in ion-beam irradiated DNA. The final section presents radiation-produced electron-mediated site-specific formation of oxidative neutral aminyl radicals from azidonucleosides and the evidence of radiosensitization provided by these aminyl radicals in azidonucleoside-incorporated breast cancer cells.

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Simultaneous alteration ofde novoandsalvagepathway to the deoxynucleoside triphosphate pool by (E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) and zidovudine (AZT) results in increased radiosensitivityin vitro

Cited by 11 publications

References 31 publications

DNA damage and neurotoxicity of chronic alcohol abuse

DNA damage and neurotoxicity of chronic alcohol abuse

Formation of Aminyl Radicals on Electron Attachment to AZT: Abstraction from the Sugar Phosphate Backbone versus One-Electron Oxidation of Guanine

Reaction of Electrons with DNA: Radiation Damage to Radiosensitization

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