Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: The role of dna base damage

Breimer, Lars H.

doi:10.1002/mc.2940030405

Cited by 334 publications

(106 citation statements)

References 109 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, it has been reported that · OH reacts with purines to form mutagenic 8-hydroxypurine and putatively nonmutagenic formamidopyrimidine lesions. The formamidopyrimidine lesions inhibit DNA synthesis, likely modulating the mutagenic potential of the 8-hydroxypurine lesions, which would suggest that the ratio of these oxidized bases is biologically important [72][73][74]. Because it has the lowest oxidation potential of the four DNA bases, guanine is the most readily oxidized base through free radical attack of C8 leading to the formation of 8OHG under elevated oxygen tension and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (fapyguanine) under conditions of reduced oxygen tension [68,70,75].…”

Section: Dna Oxidation and Repairmentioning

confidence: 99%

Nucleic acid oxidation in Alzheimer disease

Moreira

Nunomura

Nakamura

et al. 2008

Free Radical Biology and Medicine

187

113

View full text Add to dashboard Cite

Increasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. In Alzheimer disease, however, an accumulation of nucleic acid oxidation is observed, indicating an increased level of oxidative stress and/or a decreased capacity to repair the nucleic acid damage. In this review, we present data supporting the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed.

show abstract

Section: Dna Oxidation and Repairmentioning

confidence: 99%

Nucleic acid oxidation in Alzheimer disease

Moreira

Nunomura

Nakamura

et al. 2008

Free Radical Biology and Medicine

187

113

View full text Add to dashboard Cite

show abstract

“…Reactive oxygen species leading to oxidatively modified DNA bases have been implicated in a wide variety of pathophysiological states, including aging, arthritis, tumor induction and promotion, and atherosclerosis (1,2). Oxidized base lesions in DNA are repaired via a highly conserved base excision repair (BER) 3 pathway (3,4) that is initiated with excision of the damaged base by DNA glycosylases, followed by DNA strand cleavage at the lesion site.…”

mentioning

confidence: 99%

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Banerjee

Mandal

Das

et al. 2011

Journal of Biological Chemistry

128

150

View full text Add to dashboard Cite

Preferential repair of bulky DNA adducts from the transcribed genes via nucleotide excision repair is well characterized in mammalian cells. However, definitive evidence is lacking for similar repair of oxidized bases, the major endogenous DNA lesions. Here we show that the oxidized base-specific human DNA glycosylase NEIL2 associates with RNA polymerase II and the transcriptional regulator heterogeneous nuclear ribonucleoprotein-U (hnRNP-U), both in vitro and in cells. NEIL2 immunocomplexes from cell extracts preferentially repaired the mutagenic cytosine oxidation product 5-hydroxyuracil in the transcribed strand. In a reconstituted system, we also observed NEIL2-initiated transcription-dependent base excision repair of 5-hydroxyuracil in the transcribed strand, with hnRNP-U playing a critical role. Chromatin immunoprecipitation/reimmunoprecipitation studies showed association of NEIL2, RNA polymerase II, and hnRNP-U on transcribed but not on transcriptionally silent genes. Furthermore, NEIL2-depleted cells accumulated more DNA damage in active than in silent genes. These results strongly support the preferential role of NEIL2 in repairing oxidized bases in the transcribed genes of mammalian cells.

show abstract

“…The potential exposure to genotoxic agents, both physical and chemical, can produce, depending on the type of injury induced on DNA, chromosomal abnormalities such as chromosomal and/or aberrations, making these agents clastogens [8,9]. DNA damage is an indicator of exposure to agents that affect it, and it is commonly measured by the breakage of single or double chains as chromosomal aberrations [10,11]. The latter are easily observed by structural changes in the metaphase of the cell cycle, which are caused by breakage (clastogenic processes) of unrepaired or poorly repaired DNA chains [12].…”

Section: Introductionmentioning

confidence: 99%

Influence of thermodynamic parameters on the genotoxicity of bioactive phenolic compounds present in food

Guardado

Matos

Santana

et al. 2013

Proceedings of the 17th International Electronic Conference on Synthetic Organic Chemistry

View full text Add to dashboard Cite

The effects in health of food rich in phenols require currently studies related to safety. It has been shown that these compounds can present dual activity (antioxidant/pro-oxidant effects). In this sense, this work it is focused on an in silico study to determine the relationships of various thermodynamic parameters to genotoxicity (GT) of phenolic compounds: flavonoids, cinnamic acids and coumarins. The fundamental basis of the extra-thermodynamic methodology establishes that the structure of the bioactive molecule is a function of certain local and global properties. It was modeled the influence of local and global parameters that characterize the structure (hydrophobic, steric, electronic, and log P properties) relative to the clastogenic capacity (chromosome aberration generated by DNA damage due to its pro-oxidant activity). To achieve these objectives they were used ChemDraw, MODESLAB and STATISTIC software.They were identified properties influencing the genetic damage caused by the studied compounds with pro-oxidant activity, expressed through different Multivariate Linear Regression (MLR) statistical models. It was shown that steric (Sterimol, L) and hydrophobic (π) properties presented greater influence than the electronic properties (Hammett constant, σ*).Regarding the global property analysed, it was found that a decrease in the log P is associated with increased DNA damage by clastogenicity. The results allow us to produce an analysis of structure-toxicity relationship in designing strategies for nutraceuticals, functional foods and novel drug with such phenolic compounds on their structure.

show abstract

Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: The role of dna base damage

Cited by 334 publications

References 109 publications

Nucleic acid oxidation in Alzheimer disease

Nucleic acid oxidation in Alzheimer disease

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Influence of thermodynamic parameters on the genotoxicity of bioactive phenolic compounds present in food

Contact Info

Product

Resources

About