Base Excision Repair, the Redox Environment and Therapeutic Implications

Storr, Sarah J.; Škandík, Martin

doi:10.2174/1874-470211205010088

Cited by 10 publications

(12 citation statements)

References 146 publications

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“…Fe 2+ reacts with H 2 O 2, producing site-specific hydroxyl radical (HO•), damaging DNA bases as well as the sugar/phosphate backbone of DNA ( 11 ). The base excision repair pathway is the major system for repair of oxidative-induced DNA damage ( 12 ). Thus, DNA damage can be assessed by measuring γ-H2AX which is upregulated in the presence of double-strand breaks.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

et al. 2015

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The toxicity of pharmacological ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Since pancreatic cancer cells are sensitive to H2O2 generated by ascorbate they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacological ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in non-tumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacological ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacological ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

et al. 2015

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“…Нарушение пути эксцизионной репарации ДНК должно способствовать накоплению окислительного повреждения ДНК, что приведет к увеличению мутагенных изменений. Следует отметить, что истощение глутатиона из-за накопления фумарилацетоацетата, вероятно, косвенно влияет на репарацию ДНК, так как для этого процесса также важен окислительно-восстановительный гомеостаз [31,32]. В отличие от фумарилацетоацетата сукцинилацетон не оказывает мутагенного воздействия на ДНК [24], и не доказано, что он оказывает ингибирующее действие на ДНК-гликозилазы [29].…”

Section: оригинальные статьиunclassified

Hereditary tyrosinemia type 1 in children

Волынец

Никитин

Skvortsova³

2019

Ross. vestn. perinatol. pediatr.

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Hereditary metabolic disorders include a group of diseases (more than 400) when a defect of a particular gene changes the metabolic process leading either to the accumulation of unwanted metabolites, or to a deficiency of a substance. This group also includes hereditary tyrosinemia type 1, a severe defect of tyrosine metabolism caused by deficiency of fumarylacetoacetate hydrolase (FAH) – the last enzyme of tyrosine catabolic pathway. Tyrosinemia type 1 is an autosomal recessive disorder. This paper presents a review of literature on the current state of diagnosticis and approaches to treatment of tyrosinemia using nitisinone and a low-protein diet, as well as the analysis of clinical manifestations and laboratory diagnostics of hereditary tyrosinemia type 1 in 17 children.

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“…This involves electrons generated from the TCA [203]. ROS can also be produced as part of the inflammatory response by neutrophils, eosinophils and macrophages [209]. In addition, ROS may also be generated by exogenous agents such as UV exposure, ionising radiation, carcinogenic compounds and redox-cycling drugs [210].…”

Section: 102! ! Synthetic!lethality!and!the!mmr!pathway!mentioning

confidence: 99%

“…The hydroxyl radical can also attack all five carbons of 2'-deoxyribose and further processing of these lesions yields products incorporated within DNA, released from DNA or broken DNA strands bound to DNA. These lesions then have the potential to form DNA strand breaks[205,209]. 8-oxoG is the most stable DNA lesion and can mispair with adenine[124,125] and less frequently it can pair with the original cytosine[217] during DNA replication.…”

mentioning

confidence: 99%

“…They established that each method had its own weaknesses and strengths but some of the chromatographic methods displayed artefactual oxidation whilst the immunoassays lacked specificity. The study group concluded that there is still need for an alternative validated method to be developed to measure these oxidative lesions[245].BER is largely responsible for the repair of oxidative DNA damage and to a lesser extent NER[209]. Both these pathways differ in the size of lesions that they repair and function by excising DNA lesions before instigating polymerase and ligase activity to fill in the resultant gap[246,247].…”

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confidence: 99%

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Targeting the mitochondria for the treatment of MLH1-deficient disease.

Rashid¹,

Bridge²,

Yao

et al. 2016

JCO

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I, Sukaina Rashid confirm that the research included within this thesis is my own work or that where it has been carried out in collaboration with, or supported by others, that this is duly acknowledged below and my contribution indicated. Previously published material is also acknowledged below. I attest that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge break any UK law, infringe any third party's copyright or other Intellectual Property Right, or contain any confidential material. I accept that the College has the right to use plagiarism detection software to check the electronic version of the thesis. I confirm that this thesis has not been previously submitted for the award of a degree by this or any other university.

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Base Excision Repair, the Redox Environment and Therapeutic Implications

Cited by 10 publications

References 146 publications

Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

Hereditary tyrosinemia type 1 in children

Targeting the mitochondria for the treatment of MLH1-deficient disease.

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