scholarly journals Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications

2021 ◽  
Vol 22 (20) ◽  
pp. 10969
Author(s):  
Daniel Desaulniers ◽  
Paule Vasseur ◽  
Abigail Jacobs ◽  
M. Cecilia Aguila ◽  
Norman Ertych ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Hazard Assessment ◽  
Integrated Approach ◽  
Epigenetic Mechanisms ◽  
Cancer Hallmarks ◽  
Cell Functions ◽  
Chemical Hazard ◽  
Chemical Carcinogenicity ◽  
Covalent Modifications

Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health.

scholarly journals DNA methylation and retinal degenerative diseases: at the crossroad between genes and diet

2020 ◽  
Vol 53 (383) ◽  
pp. MISC1-MISC3
Author(s):  
Andrea Maugeri
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Integrated Approach ◽  
Dietary Factors ◽  
Epigenetic Mechanisms ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Significant Difference ◽  
Retinal Degenerative Diseases ◽  
The Impact

Retinal degenerative diseases are the leading causes of blindness and low vision among working-age and older adults worldwide, with 170 and 130 million individuals suffering from age-related macular degeneration (AMD) and diabetic retinopathy, respectively. Although several studies began to show benefits from dietary interventions against retinal degenerative disease, an integrated approach is needed to understand molecular mechanisms underpinning the protective or risky effect of dietary factors. A specific area of research that elucidates mechanisms involved in gene-diet interaction is the Nutri-epigenomics, the study of the impact of diet on gene expression by modulating epigenetic mechanisms. The present research investigated the role of DNA methylation – one of the most commonly analysed epigenetic mechanisms - in the pathophysiology of retinal degenerative diseases, by exploiting a multiple integrated approach. In vitro studies initially helped us to understand how pathological features of retinal degeneration (e.g. oxidative stress, inflammation and hyperglycaemia) modulated functions of enzymes involved in the methylation of Long Interspersed Nuclear Element 1 (LINE-1) sequences in retinal cells. We also proved that some nutrients (e.g. resveratrol and curcumin) might counteract these effects and restore DNA methylation level in retinal cells under oxidative, inflammatory and high glucose conditions. We further analysed whether LINE-1 methylation level differed between patients with AMD and controls without posterior segment eye diseases. Interestingly, we noted a significant difference between the two groups, with higher LINE-1 methylation level in blood samples from AMD patients. This evidence -albeit promising for biomarker discovery- requires confirmation by further large-size prospective studies taking into account different factors. Our research, in fact, also suggested that the risk of retinal degenerative diseases derives from the combination of genetic risk variants, clinical characteristics, environmental exposures and unhealthy lifestyles, which in turn are interrelated. Thus, it would be interesting to study how the exposome -the totality of exposures individuals experience over the course of life- might induce epigenetic mechanisms able to reduce or increase the risk for retinal degenerative diseases.

scholarly journals DNA methylation: dynamic and stable regulation of memory

2011 ◽  
Vol 2 (6) ◽  
pp. 459-467 ◽  
Author(s):  
Thomas Vaissière ◽  
Courtney A. Miller
Keyword(s):  
Dna Methylation ◽  
Transcriptional Regulation ◽  
Learning And Memory ◽  
Gene Transcription ◽  
Histone Modifications ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Central Process ◽  
Recent Advances ◽  
Epigenetic Events

AbstractEpigenetic mechanisms have emerged as a central process in learning and memory. Histone modifications and DNA methy­lation are epigenetic events that can mediate gene transcription. Interesting features of these epigenetic changes are their transient and long lasting potential. Recent advances in neuroscience suggest that DNA methylation is both dynamic and stable, mediating the formation and maintenance of memory. In this review, we will further illustrate the recent hypothesis that DNA methylation participates in the transcriptional regulation necessary for memory.

scholarly journals The role of histone modifications and DNA methylation in renal cell carcinoma development

2012 ◽  
Vol 10 (3) ◽  
pp. 59-76
Author(s):  
Lilia R Kutlyeva ◽  
Irina R Gilayzova ◽  
Rita I Khusainova ◽  
Elsa K Khusnutdinova
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Gene Regulation ◽  
Cell Carcinoma ◽  
Genomic Imprinting ◽  
Histone Modifications ◽  
Renal Cell ◽  
Human Cancer ◽  
Epigenetic Mechanisms

Epigenetic mechanisms of gene regulation play a key role in carcinogenesis. This review will focus on the recent advances of epigenetic investigations in the development of human cancer. The role of histone modifications, genomic imprinting and DNA methylation in renal cell carcinoma development and progression will be considered.

scholarly journals The Use of Natural Products of Epigenetic Modulators in Anti-Cancer Drug Studies

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 41
Author(s):  
Demokan
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Natural Products ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanisms ◽  
Expression Of Genes ◽  
Anti Cancer

The natural products obtained from plants, bacteria, fungi and marine have been used in the treatment of human diseases throughout the centuries. These compounds of them also interfere with the expression of genes by influencing epigenetic mechanisms. Recent researches showed significant outcomes suggesting that epigenetic silencing of the main regulatory genesis a sign of cancer onset and its progression. Epigenetic mechanisms that regulate expression of genes without mutation in the DNA are carried through DNA methylation, histone modification, chromatin remodeling and RNA interference. DNA methylation observed in the promoter regions of genes and prevents binding of the transcription factors by suppressing gene expression or by altering the nucleosome package of DNA, and may also directly inhibit transcription. Plant based products, such as curcumin, flavonoids, genistein, have been shown to exhibit cytostatic and apoptotic activities by influencing DNA methylation-based gene expression regulation in tumor cells. Additionally, natural products such as sulforaphane, retinoic acid, cucurbitacin B, casein Q, parthenolide, folate, cobalamin, pyridoxine and methionine also are used as anti-cancer agents based on DNA methylation. On the other hand, microRNAs (miRNAs) play a particular role in the epigenetic regulation of gene expression in post-transcription and post-translation processes. Quercetin, tryptolide, and honokiol are the natural compounds used in miRNA based agents. Histone modifications, which also affect the chromatin structure, play an important role in the initiation and progression of carcinogenesis as well as regulation of gene expression. As expected particular inhibitors of histone acetyltransferases (HATs) and histone deacetylase (HDAC) enzymes which are responsible of histone modifications have been developed for epigenetic intervention in cancer treatment. Numerous natural compounds are known to affect histone-modifying enzymes; such as romidepsin, epigallocatechingallate (EGCG), daidzein, sulphorafane, glucoraphanin, parthenolide, triptolide, sinapinic acid. Natural epigenetic modulators developed for epigenetic mechanisms enable the destruction of apoptotic, necrotic or autophagic pathways of tumor cells. Beside epigenetic mechanisms, these products exert their effects through influencing the cell cycle, DNA repair, and epigenetic mechanisms which modulate gene expression. More extensive in vitro and in vivo studies are required to investigate the effect of natural product-based epigenetic agents which seems to be very promising for future cancer treatment approaches.

scholarly journals Regulation Is in the Air: The Relationship between Hypoxia and Epigenetics in Cancer

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 300 ◽  
Author(s):  
Diego Camuzi ◽  
Ísis de Amorim ◽  
Luis Ribeiro Pinto ◽  
Leonardo Oliveira Trivilin ◽  
André Mencalha ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Mechanisms ◽  
Prolyl Hydroxylases ◽  
Metabolic Intermediates ◽  
Cancer Hallmarks ◽  
Proliferation And Apoptosis ◽  
Histone Modifiers ◽  
Non Coding Rnas ◽  
Epigenetic Patterns ◽  
The Relationship

Hypoxia is an inherent condition of tumors and contributes to cancer development and progression. Hypoxia-inducible factors (HIFs) are the major transcription factors involved in response to low O2 levels, orchestrating the expression of hundreds of genes involved in cancer hallmarks’ acquisition and modulation of epigenetic mechanisms. Epigenetics refers to inheritable mechanisms responsible for regulating gene expression, including genes involved in the hypoxia response, without altering the sequence of DNA bases. The main epigenetic mechanisms are DNA methylation, non-coding RNAs, and histone modifications. These mechanisms are highly influenced by cell microenvironment, such as O2 levels. The balance and interaction between these pathways is essential for homeostasis and is directly linked to cellular metabolism. Some of the major players in the regulation of HIFs, such as prolyl hydroxylases, DNA methylation regulators, and histone modifiers require oxygen as a substrate, or have metabolic intermediates as cofactors, whose levels are altered during hypoxia. Furthermore, during pathological hypoxia, HIFs’ targets as well as alterations in epigenetic patterns impact several pathways linked to tumorigenesis, such as proliferation and apoptosis, among other hallmarks. Therefore, this review aims to elucidate the intricate relationship between hypoxia and epigenetic mechanisms, and its crucial impact on the acquisition of cancer hallmarks.

scholarly journals Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update

2021 ◽  
Vol 14 (6) ◽  
pp. 491
Author(s):  
Pía Loren ◽  
Nicolás Saavedra ◽  
Kathleen Saavedra ◽  
Tomás Zambrano ◽  
Patricia Moriel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Death ◽  
Side Effects ◽  
Signaling Pathways ◽  
Solid Tumors ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Epigenetic Mechanisms ◽  
Non Coding Rnas ◽  
New Strategies

Cisplatin is an antineoplastic drug used for the treatment of many solid tumors. Among its various side effects, nephrotoxicity is the most detrimental. In recent years, epigenetic regulation has emerged as a modulatory mechanism of cisplatin-induced nephrotoxicity, involving non-coding RNAs, DNA methylation and histone modifications. These epigenetic marks alter different signaling pathways leading to damage and cell death. In this review, we describe how different epigenetic modifications alter different pathways leading to cell death by apoptosis, autophagy, necroptosis, among others. The study of epigenetic regulation is still under development, and much research remains to fully determine the epigenetic mechanisms underlying cell death, which will allow leading new strategies for the diagnosis and therapy of this disease.

scholarly journals Epigenetic regulation of peroxiredoxins: Implications in the pathogenesis of cancer

2016 ◽  
Vol 242 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Suet-Hui Ow ◽  
Pei-Jou Chua ◽  
Boon-Huat Bay
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Histone Deacetylases ◽  
Epigenetic Mechanisms ◽  
Epigenetic Regulators ◽  
Future Treatments ◽  
Peroxiredoxin I ◽  
Reversible Nature

Peroxiredoxin I to VI (PRX I–VI), a family of highly conserved antioxidants, has been implicated in numerous diseases. There have been reports that PRXs are expressed aberrantly in a variety of tumors, implying that they could play an important role in carcinogenesis. Epigenetic mechanisms such as DNA methylation, histone modifications, and microRNAs have been reported to modulate expression of PRXs. In addition, the use of epigenetic regulators, such as histone deacetylases, has been demonstrated to restore PRX to normal levels, indicating that the reversible nature of epigenetics can be exploited for future treatments.

scholarly journals Epigenetic determinants in rheumatoid arthritis: the influence of DNA methylation and histone modifications

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Bogdan Kolarz ◽  
Maria Majdan
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Histone Modifications ◽  
Histone Deacetylases ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Genetic Changes ◽  
Post Translational Modifications ◽  
Methylation Of Dna

Epigenetics is a field of science which describes external and environmental modifications to DNA without altering their primary sequences of nucleotides. Contrary to genetic changes, epigenetic modifications are reversible. The epigenetic changes appear as a result of the influence of external factors, such as diet or stress. Epigenetic mechanisms alter the accessibility of DNA by methylation of DNA or post-translational modifications of histones (acetylation, methylation, phosphorylation, ubiquitinqation). The extent of DNA methylation depends on the balance between DNA methyltransferases and demethylases. The main histone modifications are stimulated by K-acetyltransferases, histone deacetylases, K-metyltransferases and K-demethylases. There is proof that environmental modifications of this enzymes regulate immunological processes including autoimmunity in rheumatoid arthritis (RA). In this work we present epigenetic mechanisms involved in RA pathogenesis and a range of research presenting the possible impact of its modification in RA patients.

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