Towards a comprehensive view of 8-oxo-7,8-dihydro-2’-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability

Gorini, Francesca; Scala, Giovanni; Cooke, Marcus S.; Majello, Barbara; Amente, Stefano

doi:10.1016/j.dnarep.2020.103027

Cited by 43 publications

(37 citation statements)

References 178 publications

(223 reference statements)

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“…H 2 O 2 treatment can directly induce DNA strand breaks as well as formation of oxidized purines (Poetsch 2020 ). Oxidized purines such as 8-oxodG can be converted to apurinic (AP) sites, which are prone to single strand break formation, which is also further enabled during the comet assay procedure (Cappelli et al 2000 ; Gorini et al 2021 ). Thus, H 2 O 2 induced lesions are subject to base excision and partly to nucleotide excision (Dizdaroglu et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Cell survival after DNA damage in the comet assay

2021

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The comet assay is widely used in basic research, genotoxicity testing, and human biomonitoring. However, interpretation of the comet assay data might benefit from a better understanding of the future fate of a cell with DNA damage. DNA damage is in principle repairable, or if extensive, can lead to cell death. Here, we have correlated the maximally induced DNA damage with three test substances in TK6 cells with the survival of the cells. For this, we selected hydrogen peroxide (H2O2) as an oxidizing agent, methyl methanesulfonate (MMS) as an alkylating agent and etoposide as a topoisomerase II inhibitor. We measured cell viability, cell proliferation, apoptosis, and micronucleus frequency on the following day, in the same cell culture, which had been analyzed in the comet assay. After treatment, a concentration dependent increase in DNA damage and in the percentage of non-vital and apoptotic cells was found for each substance. Values greater than 20–30% DNA in tail caused the death of more than 50% of the cells, with etoposide causing slightly more cell death than H2O2 or MMS. Despite that, cells seemed to repair of at least some DNA damage within few hours after substance removal. Overall, the reduction of DNA damage over time is due to both DNA repair and death of heavily damaged cells. We recommend that in experiments with induction of DNA damage of more than 20% DNA in tail, survival data for the cells are provided.

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Section: Discussionmentioning

confidence: 99%

Cell survival after DNA damage in the comet assay

2021

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“…By giving consideration to the above, various mechanisms together, we are building a better picture of how ‘damage’, or perhaps more accurately ‘modifications’, are involved in the disease process. This is leading to a better understanding of how oxidative stress, DNA damage/genomic instability, gene regulatory mechanisms and DNA repair, can influence the cellular redox status, maintain homeostasis, or contribute to, or prevent, the development or progression of various diseases (discussed in Mikhed et al [ 27 ], and Gorinin et al [ 28 ]), which include cancer [ 29 , 30 ], Alzheimer's disease [ 31 ], and other neurodegenerative diseases [ 32 ], and also ageing [ 33 , 34 ].…”

Section: Formation Repair and Consequences Of Damage To Nucleic Acidsmentioning

confidence: 99%

Biomarkers of nucleic acid oxidation – A summary state-of-the-art

Chao

Evans

et al. 2021

Redox Biology

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Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. Increasingly, interest is also focusing upon the effects of damage to the other nucleic acids, RNA and the (2′-deoxy-)ribonucleotide pools, and evidence is growing that these too may have an important role in disease. LC-MS/MS has the ability to provide absolute quantification of specific biomarkers, such as 8-oxo-7,8-dihydro-2′-deoxyGuo (8-oxodG), in both nuclear and mitochondrial DNA, and 8-oxoGuo in RNA. However, significant quantities of tissue are needed, limiting its use in human biomonitoring studies. In contrast, the comet assay requires much less material, and as little as 5 μL of blood may be used, offering a minimally invasive means of assessing oxidative stress in vivo , but this is restricted to nuclear DNA damage only. Urine is an ideal matrix in which to non-invasively study nucleic acid-derived biomarkers of oxidative stress, and considerable progress has been made towards robustly validating these measurements, not least through the efforts of the European Standards Committee on Urinary (DNA) Lesion Analysis. For urine, LC-MS/MS is considered the gold standard approach, and although there have been improvements to the ELISA methodology, this is largely limited to 8-oxodG. Emerging DNA adductomics approaches, which either comprehensively assess the totality of adducts in DNA, or map DNA damage across the nuclear and mitochondrial genomes, offer the potential to considerably advance our understanding of the mechanistic role of oxidatively damaged nucleic acids in disease.

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“…Interestingly, there is also a link between DNA damage and epigenetics. In this way, it has been found that 8-oxo-7,8-dihydro-2 -deoxyguanosine (8-oxodG) may modulate epigenetic regulation of gene expression [161].…”

Section: Epigenomicsmentioning

confidence: 99%

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

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Towards a comprehensive view of 8-oxo-7,8-dihydro-2’-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability

Cited by 43 publications

References 178 publications

Cell survival after DNA damage in the comet assay

Cell survival after DNA damage in the comet assay

Biomarkers of nucleic acid oxidation – A summary state-of-the-art

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

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