Special Issue "Role of Oxidatively-Induced DNA Damage in Carcinogenesis"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 April 2014)

Special Issue Editor

Guest Editor
Dr. Alexandros G. Georgakilas

Biophysics/DNA damage and Repair Lab, Physics Department, National Technical University of Athens, Iroon Polytechneiou 9, Zografou Campus, Athens 15780, Greece
Website | E-Mail
Fax: +30 210 772 3025
Interests: radiation biology; cancer biology; DNA damage and repair; oxidative stress; carcinogenesis

Special Issue Information

Dear Colleagues,

Oxidative stress and all related effects in the cell like protein and DNA damage, mutagenesis, inactivation of DNA damage response pathways, epigenetic changes and further more importantly genomic instability and malignant transformation have gained through the years an increased attention. It is of great necessity to clarify and underline the significance and ‘real’ relevance of oxidatively-induced DNA damage in the initiation of carcinogenesis.
We would like to invite manuscripts that aim to elucidate the role(s) of oxidative stress related DNA damage of all forms in carcinogenesis and for various types of cancers like breast, brain, lung, prostate etc. We are particularly interested in manuscripts deciphering the mechanisms and pathways that oxidative DNA damage can lead to mutation and inactivation of DNA repair and apoptotic genes and epigenetic changes and new therapy tools. We are also welcome manuscripts focusing on the synergistic effects between inflammation, oxidative stress and tumorigenesis in humans and to potential anti-oxidant and anti-inflammatory pathways that reduce cancer risk. By devoting a special issue just on oxidative stress-related carcinogenesis, we hope to join forces and enhance the knowledge in the specific field and above all promote the new era of therapeutic discoveries targeting cancer through the diminution of oxidative stress and inflammation.

Dr. Alexandros Georgakilas
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).

Keywords

  • oxidative stress
  • DNA damage
  • inflammation
  • DNA repair inactivation
  • DNA damage response
  • genomic instability
  • carcinogenesis
  • antioxidant therapies

Published Papers (7 papers)

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Research

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Open AccessArticle Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2
Cancers 2013, 5(3), 959-984; doi:10.3390/cancers5030959
Received: 3 June 2013 / Revised: 12 July 2013 / Accepted: 18 July 2013 / Published: 26 July 2013
Cited by 2 | PDF Full-text (1096 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2
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We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)

Review

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Open AccessReview DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment
Cancers 2014, 6(3), 1597-1614; doi:10.3390/cancers6031597
Received: 14 May 2014 / Revised: 2 July 2014 / Accepted: 18 July 2014 / Published: 5 August 2014
Cited by 19 | PDF Full-text (851 KB) | HTML Full-text | XML Full-text
Abstract
Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and
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Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
Open AccessReview Inflammation, Cancer and Oxidative Lipoxygenase Activity are Intimately Linked
Cancers 2014, 6(3), 1500-1521; doi:10.3390/cancers6031500
Received: 16 April 2014 / Revised: 27 June 2014 / Accepted: 2 July 2014 / Published: 17 July 2014
Cited by 13 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism. An increasing number of arachidonic acid metabolites is being discovered and apart from their classically
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Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism. An increasing number of arachidonic acid metabolites is being discovered and apart from their classically recognized pro-inflammatory effects, anti-inflammatory effects are also being described in recent years. Interestingly, these lipid mediators are involved in activation of pro-inflammatory signal transduction pathways such as the nuclear factor κB (NF-κB) pathway, which illustrates the intimate link between lipid signaling and transcription factor activation. The identification of the role of arachidonic acid metabolites in several inflammatory diseases led to a significant drug discovery effort around arachidonic acid metabolizing enzymes. However, to date success in this area has been limited. This might be attributed to the lack of selectivity of the developed inhibitors and to a lack of detailed understanding of the functional roles of arachidonic acid metabolites in inflammatory responses and cancer. This calls for a more detailed investigation of the activity of arachidonic acid metabolizing enzymes and development of more selective inhibitors. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
Figures

Open AccessReview Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis
Cancers 2014, 6(2), 1208-1219; doi:10.3390/cancers6021208
Received: 16 April 2014 / Revised: 21 May 2014 / Accepted: 26 May 2014 / Published: 4 June 2014
Cited by 10 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome
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The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome stability, oxidative stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is lost or reduced in many human cancers, is a tumor suppressor and genome caretaker whose loss initiates genome instability in preneoplastic lesions. Ongoing studies are seeking more detailed understanding of the role of FHIT in the cellular response to oxidative damage. This review discusses the relationship between FHIT, reactive oxygen species production, and DNA damage in the context of cancer initiation and progression. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
Open AccessReview BRCA1 and Oxidative Stress
Cancers 2014, 6(2), 771-795; doi:10.3390/cancers6020771
Received: 19 December 2013 / Revised: 20 March 2014 / Accepted: 24 March 2014 / Published: 3 April 2014
Cited by 12 | PDF Full-text (808 KB) | HTML Full-text | XML Full-text
Abstract
The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this
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The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1’s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
Open AccessReview Oxidative Stress in the Carcinogenicity of Chemical Carcinogens
Cancers 2013, 5(4), 1332-1354; doi:10.3390/cancers5041332
Received: 16 August 2013 / Revised: 26 September 2013 / Accepted: 12 October 2013 / Published: 28 October 2013
Cited by 8 | PDF Full-text (590 KB) | HTML Full-text | XML Full-text
Abstract
This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with
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This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)
Open AccessReview PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?
Cancers 2013, 5(3), 943-958; doi:10.3390/cancers5030943
Received: 3 May 2013 / Revised: 17 July 2013 / Accepted: 19 July 2013 / Published: 26 July 2013
Cited by 30 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is
[...] Read more.
Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation. Full article
(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)

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