Mechanism of mutagenicity by 5-hydroperoxymethyl-2′-deoxyuridine, an intermediate product of ionizing radiation, in bacteria

Patel, Umesh A.; Bhimani, Ramesh; Frenkel, Krystyna

doi:10.1016/0165-7992(92)90147-a

Cited by 12 publications

(4 citation statements)

References 43 publications

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“…Among this group of oxidized pyrimidines, 5-hydroxycytosine ( , ) and 5-formyluracil ( − ) are known to induce mispair formation during DNA replication. The mechanisms by which oxidation of pyrimidines may increase the level of base mispair formation are as yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Conformation and Proton Configuration of Pyrimidine Deoxynucleoside Oxidation Damage Products in Water

Francois

Jang

Çağın

et al. 2000

Chem. Res. Toxicol.

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Emerging data strongly suggest that the oxidation of DNA bases can contribute to genomic instability. Structural changes to DNA, induced by base oxidation, may reduce the fidelity of DNA replication and interfere with sequence-specific DNA-protein interactions. We have examined the structures of a series of pyrimidine deoxynucleoside oxidation damage products in aqueous solution. The modified nucleosides studied include the deoxynucleoside derivatives of 5-hydroxyuracil, 5-hydroxycytosine, 5-(hydroxymethyl)uracil, 5-(hydroxymethyl)cytosine, 5-formyluracil, and 5-formylcytosine. The influence of base oxidation on ionization constants, sugar conformation, and tautomeric configuration has been determined on the basis of UV, proton, and nitrogen NMR spectra of the (15)N-enriched derivatives. The potential biological consequences of the structural perturbations resulting from base oxidation are discussed.

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Section: Introductionmentioning

confidence: 99%

Conformation and Proton Configuration of Pyrimidine Deoxynucleoside Oxidation Damage Products in Water

Francois

Jang

Çağın

et al. 2000

Chem. Res. Toxicol.

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“…The oxidized thymidine derivatives 5-(hydroxymethyl)-2‘-deoxyuridine and 5-formyl-2‘-deoxyuridine can be formed by endogenous DNA oxidation, and increased levels are formed as a consequence of ionizing radiation ( − ). Both have been shown to be mutagenic in vitro ( − ). Oxidation of cytosine, initially forming the glycol, with subsequent hydrolytic deamination and dehydration generates 5-hydroxyuracil ().…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Isotopically Enriched Pyrimidine Deoxynucleoside Oxidation Damage Products

LaFrancois

Fujimoto

Sowers

1998

Chem. Res. Toxicol.

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Oxidative damage to DNA is an established source of genomic instability. In this paper, we describe the synthesis and characterization of several pyrimidine deoxynucleoside oxidation damage products, enriched with stable isotopes. These products include the 2'-deoxynucleoside derivatives of 5-(hydroxymethyl)uracil, 5-formyluracil, 5-hydroxyuracil, 5-(hydroxymethyl)cytosine, 5-formylcytosine, and 5-hydroxycytosine. The common precursor is 2'-deoxy-2"-deutero[1,3-15N]uridine. Additional stable isotopes are added during functional group conversions. Characterization of these derivatives includes mass spectrometry and 1H and 15N NMR spectroscopy. Proton and nitrogen NMR studies reported here allow an examination of the influence of the modification on sugar conformation and tautomeric equilibrium, properties likely to be important in understanding the biological consequences of these DNA damage products.

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“…This unusual structure suggests 5-HMdUrd may miscode during DNA replication. Such a likelihood is further suggested by the finding that 5-HmdUrd itself and also its hydroperoxy precursor induce a high incidence of mutations in Salmonella typhimurium (58,59). These considerations may warrant more careful investigation of the mutagenicity of this lesion.…”

mentioning

confidence: 99%

Endogenous DNA adducts: Potential and paradox

Marnett¹,

Burcham²

1993

Chem. Res. Toxicol.

286

154

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Mechanism of mutagenicity by 5-hydroperoxymethyl-2′-deoxyuridine, an intermediate product of ionizing radiation, in bacteria

Cited by 12 publications

References 43 publications

Conformation and Proton Configuration of Pyrimidine Deoxynucleoside Oxidation Damage Products in Water

Conformation and Proton Configuration of Pyrimidine Deoxynucleoside Oxidation Damage Products in Water

Synthesis and Characterization of Isotopically Enriched Pyrimidine Deoxynucleoside Oxidation Damage Products

Endogenous DNA adducts: Potential and paradox

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