Pattern of hydroxyl radical addition to cytosine and 1-, 3-, 5-, and 6-substituted cytosines. Electron transfer and dehydration reactions of the hydroxyl adducts

Hazra, Dilip K.; Steenken, S.

doi:10.1021/ja00351a042

Cited by 166 publications

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“…Although more information exists regarding reactions of OH with thymine and uracil, the greater experimental controversy for site preference of OH addition to cytosine lent impetus to the choice of cytosine as a subject for these calculations. A recent paper (8) suggested that site selection of OH attack of cytosine is more discriminating than for the analogous reactions with thymine and uracil and that the major product, in opposition to expectations from the results of our previous studies on OH reactions with N heterocycles (1,2), was the species favored on account of electrophilic interactions rather than being the most electronically delocalized product. These factors contributed to the selection of cytosine as the subject for study.…”

Section: Introductioncontrasting

confidence: 82%

“…Hazra and Steenken (8) report that substitution at the N1 or N3 positions has little effect on site preference, thus implying a keto tautomeric form as shown in species 4-7 ( Fig. 1).…”

Section: Resultsmentioning

confidence: 97%

“…Hissung and Von Sonntag used pulse radiolysis with both optical and conductimetric detection techniques to conclude that 55% of OH addition occurs at the C5 position (9). This preference for attack at the C5 site is supported by Hazra and Steenken who used pulse radiolysis and the oxidative-reductive characteristics of the nascent radicals (8). These authors however found a ratio of preference for the C.5 adduct to the C6 adduct of 9: 1.…”

Section: Introductionmentioning

confidence: 98%

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AbInitio SCF MO calculations on the reaction of hydroxyl radical with cytosine

Eatock¹,

Waltz²,

Mezey³

1986

Can. J. Chem.

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. 64,914 (1986).Ab initio calculations have been carried out on the relative stabilities of various possible products of the reaction between cytosine and the OH radical. These products are of importance in modelling radiation damage to living tissues. The preferred theoretical gas-phase addition site is the C6 ring atom according to these calculations. The analysis of a series of possible contributions to solvent effects strongly suggests the predominance of intermolecular H bonds in stabilizing the experimentally observed C5 adduct.BEVERLEY G. EAToCK, WILLIAM L. WALTZ, et PAUL G. MEZEY. Can. J. Chem. 64,914 (1986).On a effectut de calculs ab initio sur les stabilitks relatives de divers produits possibles pour la rkaction de la cytosine avec le radical OH. Ces produits sont importants dans l'klaboration d'un modkle pour les dommages dfis B la radiation dans les tissus vivants. D'apr2s ces calculs thtoriques, le site prkftrt pour l'addition en phase gazeuse est l'atome de carbone C6. L'analyse d'une skrie de contributions possibles aux effets de solvant sugg2re fortement la prkdominance de liaisons hydrogknes intermoltculaires dans la stabilisation de l'adduit en C5 qui est observk expkrimentalement.[Traduit par la revue] Introduction Radiation damage to nitrogen heterocycles has attracted interest due to the relevance of such effects for biologically important systems. As an extension of studies on the reactions of OH radicals with N heterocyclic systems (pyridine, imidazole) (1, 2), we have investigated the attack of OH on the pyrimidine base cytosine. Experimental results on the reaction of OH with cytosine agree that ring addition occurs (3,4), but information on site preference for addition is obtained only by indirect methods (esr, pulse radiolysis) leaving results open to some controversy. Ab initio calculations, however, provide a direct aid to identification of favored product isomers, and have been shown to be useful in past studies, supplementing experimental results (1,2,5,6).Radiation damage to cytosine is of interest because of its status as a component of DNA. Consideration of the N bases of DNA as subjects for ab initio studies favors the pyrimidines, both because of their greater susceptibility to OH attack (7) and the simpler problem that the electronic structure of the pyrimidines represents, as compared to the purine bases. Although more information exists regarding reactions of OH with thymine and uracil, the greater experimental controversy for site preference of OH addition to cytosine lent impetus to the choice of cytosine as a subject for these calculations. A recent paper (8) suggested that site selection of OH attack of cytosine is more discriminating than for the analogous reactions with thymine and uracil and that the major product, in opposition to expectations from the results of our previous studies on OH reactions with N heterocycles (1,2), was the species favored on account of electrophilic interactions rather than being the most electronically delocalized product. These factor...

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Section: Introductioncontrasting

confidence: 82%

“…Hazra and Steenken (8) report that substitution at the N1 or N3 positions has little effect on site preference, thus implying a keto tautomeric form as shown in species 4-7 ( Fig. 1).…”

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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AbInitio SCF MO calculations on the reaction of hydroxyl radical with cytosine

Eatock¹,

Waltz²,

Mezey³

1986

Can. J. Chem.

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“…The first is via oxidative attack on the methyl group of thymine resulting in formation of an HmUra opposite adenine (11,28). The second is via deamination of 5-hydroxymethylcytosine, which could be formed in DNA as a consequence of oxidative attack on the methyl group of 5-methylcytosine (1,14). This would result in an HmUra opposite guanine.…”

mentioning

confidence: 99%

A mammalian cell line deficient in activity of the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine.

Boorstein¹,

Chiu²,

Teebor³

1992

Mol. Cell. Biol.

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We isolated a mutant mammalian cell line lacking activity for the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase (HmUra-DNA glycosylase). The mutant was isolated through its resistance to the thymidine analog 5-hydroxymethyl-2'-deoxyuridine (HmdUrd). The mutant incorporates HmdUrd into DNA to the same extent as the parent line but, lacking the repair enzyme, does not remove it. The phenotype of the mutant demonstrates that the toxicity of HmdUrd does not result from substitution of thymine in DNA by HmUra but rather from the removal via base excision of large numbers of HmUra residues in DNA. This finding elucidates a novel mechanism of toxicity for a xenobiotic nucleoside. Furthermore, the isolation of this line supports our hypothesis that the enzymatic reparability of HmUra derives not from its formation opposite adenine via the oxidation of thymine, but rather from its formation opposite guanine as a product of the oxidation and subsequent deamination of 5-methylcytosine.

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“…As our experiments were carried out in a nitrous oxide-saturated solution, the damage inflicted on DNA was primarily due to OH attack. Studies with model pyrimidine nucleic acid bases indicate that in the case of uracil, thymine, and cytosine, the 5,6 positions of the ring are most susceptible to attack by OH (30,31). This results in the generation of a radical center either at C-5 or at C-6.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Double-Strand Modification in Calf Thymus DNA in the Presence of 1,2-Dihydroxy-9,10-Anthraquinone and Its Cu(II) Complex

Das¹,

Saha²,

Mandal³

1997

Environmental Health Perspectives

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When cells or DNA is exposed to ionizing radiation, the radicals produced in the irradiated sample will modify the base-pair region of the double strands. Effects of 1,2-dihydroxy-9,10-anthraquinone (DHA) and its Cu(ll) complex on the radiation-induced modification of doublestrands in calf thymus DNA were studied using ethidium bromide as a fluorescent probe. Our results show that the Cu(ll)-DHA complex is more efficient in modifying the base-pair region in double-stranded DNA compared to free DHA.

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Pattern of hydroxyl radical addition to cytosine and 1-, 3-, 5-, and 6-substituted cytosines. Electron transfer and dehydration reactions of the hydroxyl adducts

Cited by 166 publications

References 0 publications

AbInitio SCF MO calculations on the reaction of hydroxyl radical with cytosine

AbInitio SCF MO calculations on the reaction of hydroxyl radical with cytosine

A mammalian cell line deficient in activity of the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine.

Radiation-Induced Double-Strand Modification in Calf Thymus DNA in the Presence of 1,2-Dihydroxy-9,10-Anthraquinone and Its Cu(II) Complex

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