scholarly journals Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor D. Martinez ◽  
Emily A. Vucic ◽  
Marta Adonis ◽  
Lionel Gil ◽  
Wan L. Lam
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Repair Process ◽  
Dna Methyltransferases ◽  
Health Concern ◽  
Dna Damage And Repair ◽  
Repair Mechanisms ◽  
Contaminated Drinking Water ◽  
High Concentrations ◽  
Epigenetic Patterns

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

scholarly journals The emerging role of RNAs in DNA damage repair

2017 ◽  
Vol 24 (4) ◽  
pp. 580-587 ◽  
Author(s):  
Ben R Hawley ◽  
Wei-Ting Lu ◽  
Ania Wilczynska ◽  
Martin Bushell
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Critical Role ◽  
Repair Process ◽  
Rna Molecules ◽  
Processing Enzymes ◽  
Damage Repair ◽  
New Findings ◽  
Integral Role ◽  
Repair Mechanisms

Abstract Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process. Several reports demonstrated a conserved critical role for RNA-processing enzymes and RNA molecules in DNA repair, but the biogenesis of these damage-related RNAs and their mechanisms of action remain unknown. We will explore how these new findings challenge the idea of proteins being the sole participants in the response to DNA damage and reveal a new and exciting aspect of both DNA repair and RNA biology.

Integrated Microarray-based Tools for Detection of Genomic DNA Damage and Repair Mechanisms

2017 ◽  
pp. 77-99 ◽  
Author(s):  
Patrick van Eijk ◽  
Yumin Teng ◽  
Mark R. Bennet ◽  
Katie E. Evans ◽  
James R. Powell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Dna ◽  
Dna Damage And Repair ◽  
Repair Mechanisms

scholarly journals Strategies for the evaluation of DNA damage and repair mechanisms in cancer

2017 ◽  
Vol 13 (6) ◽  
pp. 3982-3988 ◽  
Author(s):  
Gabriela Figueroa-González ◽  
Carlos Pérez-Plasencia
Keyword(s):  
Dna Damage ◽  
Dna Damage And Repair ◽  
Repair Mechanisms

Mammalian Cell DNA Damage and Repair Kinetics of Monohaloacetic Acid Drinking Water Disinfection By-Products

2009 ◽  
Vol 43 (21) ◽  
pp. 8437-8442 ◽  
Author(s):  
Yukako Komaki ◽  
Justin Pals ◽  
Elizabeth D. Wagner ◽  
Benito J. Mariñas ◽  
Michael J. Plewa
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Mammalian Cell ◽  
Water Disinfection ◽  
Dna Damage And Repair ◽  
Drinking Water Disinfection ◽  
Kinetics Of ◽  
By Products

scholarly journals Novel insights into the mode of action of 1,4-dioxane using a systems screening approach

2020 ◽  
Author(s):  
Georgia Charkoftaki ◽  
Jaya Prakash Golla ◽  
Alvaro Santos-Neto ◽  
David J. Orlicky ◽  
Rolando Garcia-Milian ◽  
...  
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Immunohistochemical Analysis ◽  
The United States ◽  
Environmental Chemicals ◽  
Dna Double Strand Breaks ◽  
Dna Damage And Repair ◽  
Mechanisms Of Toxicity ◽  
Novel Approach ◽  
Histopathological Studies

Abstract1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.

Role of DNA damage and repair mechanisms in uterine fibroid/leiomyomas: a review

2020 ◽  
Author(s):  
Sneh M Toprani ◽  
Varsha Kelkar Mane
Keyword(s):  
Dna Damage ◽  
Molecular Mechanisms ◽  
Healthcare Sector ◽  
Clinical Aspects ◽  
Dna Damage And Repair ◽  
Myometrial Cells ◽  
Mutational Burden ◽  
The World ◽  
Repair Mechanisms

Abstract There has been a significant annual increase in the number of cases of uterine leiomyomas or fibroids (UF) among women of all races and ages across the world. A fortune is usually spent by the healthcare sector for fibroid-related treatments and management. Molecular studies have established the higher mutational heterogeneity in UF as compared to normal myometrial cells. The contribution of DNA damage and defects in repair responses further increases the mutational burden on the cells. This in turn leads to genetic instability, associated with cancer risk and other adverse reproductive health outcomes. Such and many more growing bodies of literature have highlighted the genetic/molecular, biochemical and clinical aspects of UF; none the less there appear to be a lacuna bridging the bench to bed gap in addressing and preventing this disease. Presented here is an exhaustive review of not only the molecular mechanisms underlying the predisposition to the disease but also possible strategies to effectively diagnose, prevent, manage, and treat this disease.

Hexavalent Chromium-Induced DNA Damage and Repair Mechanisms

2008 ◽  
Vol 23 (1) ◽  
Author(s):  
Sandra S. Wise ◽  
Amie L. Holmes ◽  
John Pierce Wise, Sr.
Keyword(s):  
Dna Damage ◽  
Hexavalent Chromium ◽  
Dna Damage And Repair ◽  
Repair Mechanisms

Identification of dose-dependent DNA damage and repair responses from subchronic exposure to 1,4-dioxane in mice using a systems analysis approach

2021 ◽  
Author(s):  
Georgia Charkoftaki ◽  
Jaya Prakash Golla ◽  
Alvaro Santos-Neto ◽  
David J Orlicky ◽  
Rolando Garcia-Milian ◽  
...  
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Immunohistochemical Analysis ◽  
The United States ◽  
Environmental Chemicals ◽  
Dna Double Strand Breaks ◽  
Dna Damage And Repair ◽  
Mechanisms Of Toxicity ◽  
Novel Approach ◽  
Histopathological Studies

Abstract 1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.

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