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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) | Viewed by 89390

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Special Issue Editor

Prof. Dr. Alexandros Georgakilas

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Guest Editor

Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 15780 Athens, Greece
Interests: radiation biology; DNA damage and repair; clustered DNA lesions; systemic effects of radiation; systems biology
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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

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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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1096 KiB

Open AccessArticle

Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

by Shyh-Shin Chiou, Sophie Sheng-Wen Wang, Deng-Chyang Wu, Ying-Chu Lin, Li-Pin Kao, Kung-Kai Kuo, Chun-Chieh Wu, Chee-Yin Chai, Cheng-Lung Steve Lin, Cheng-Yi Lee, Yu-Mei Liao, Kenly Wuputra, Ya-Han Yang, Shin-Wei Wang, Chia-Chen Ku, Yukio Nakamura, Shigeo Saito, Hitomi Hasegawa, Naoto Yamaguchi, Hiroyuki Miyoshi, Chang-Sheng Lin, Richard Eckner and Kazunari K. Yokoyama Show full author list Hide full author list

Cancers 2013, 5(3), 959-984; https://doi.org/10.3390/cancers5030959 - 26 Jul 2013

Cited by 20 | Viewed by 9038

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 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)

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Review

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851 KiB

Open AccessReview

DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

by Gemma Bridge, Sukaina Rashid and Sarah A. Martin

Cancers 2014, 6(3), 1597-1614; https://doi.org/10.3390/cancers6031597 - 05 Aug 2014

Cited by 95 | Viewed by 12295

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 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)

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Open AccessReview

Inflammation, Cancer and Oxidative Lipoxygenase Activity are Intimately Linked

by Rosalina Wisastra and Frank J. Dekker

Cancers 2014, 6(3), 1500-1521; https://doi.org/10.3390/cancers6031500 - 17 Jul 2014

Cited by 130 | Viewed by 12054

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 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)

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Open AccessReview

Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis

by Jenna R. Karras, Carolyn A. Paisie and Kay Huebner

Cancers 2014, 6(2), 1208-1219; https://doi.org/10.3390/cancers6021208 - 04 Jun 2014

Cited by 23 | Viewed by 9081

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 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)

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Open AccessReview

BRCA1 and Oxidative Stress

by Yong Weon Yi, Hyo Jin Kang and Insoo Bae

Cancers 2014, 6(2), 771-795; https://doi.org/10.3390/cancers6020771 - 03 Apr 2014

Cited by 41 | Viewed by 11846

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 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)

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Open AccessReview

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

by Anna Kakehashi, Min Wei, Shoji Fukushima and Hideki Wanibuchi

Cancers 2013, 5(4), 1332-1354; https://doi.org/10.3390/cancers5041332 - 28 Oct 2013

Cited by 41 | Viewed by 9579

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 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)

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Open AccessReview

PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

by Amanda F. Swindall, Jennifer A. Stanley and Eddy S. Yang

Cancers 2013, 5(3), 943-958; https://doi.org/10.3390/cancers5030943 - 26 Jul 2013

Cited by 93 | Viewed by 24621

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 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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