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Helen B. Patrzyc

Bio: Helen B. Patrzyc is an academic researcher from Roswell Park Cancer Institute. The author has contributed to research in topics: DNA damage & DNA. The author has an hindex of 13, co-authored 33 publications receiving 449 citations.
Topics: DNA damage, DNA, Nucleoside, Thymine, Guanine

Papers
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Journal ArticleDOI
TL;DR: The singlet oxygen-induced lesion was isolated from a short synthetic oligomer after exposure to UVA radiation in the presence of methylene blue and could be enzymatically excised from the oligomer in the form of a modified dinucleoside monophosphate.
Abstract: Singlet oxygen, hydrogen peroxide, hydroxyl radical and hydrogen peroxide are the reactive oxygen species (ROS) considered most responsible for producing oxidative stress in cells and organisms. Singlet oxygen interacts preferentially with guanine to produce 8-oxo-7,8-dihydroguanine and spiroiminodihydantoin. DNA damage due to the latter lesion has not been detected directly in the DNA of cells exposed to singlet oxygen. In this study, the singlet oxygen-induced lesion was isolated from a short synthetic oligomer after exposure to UVA radiation in the presence of methylene blue. The lesion could be enzymatically excised from the oligomer in the form of a modified dinucleoside monophosphate. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), the singlet oxygen lesion was detected in the form of modified dinucleoside monophosphates in double-stranded DNA and in the DNA of HeLa cells exposed to singlet oxygen. Pentamer containing the singlet oxygen-induced lesion and an isotopic label was synthesized as an internal standard for quantifying the lesion and served as well as for correcting for losses of product during sample preparation.

77 citations

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TL;DR: It was possible to show directly that double lesions are formed in irradiated calf thymus DNA using reference oligomer containing a specific double lesion and employing liquid chromatography-mass spectrometry (LC-MS), which confirmed the formation of such lesions in polymer DNA.
Abstract: Box, H. C., Patrzyc, H. B., Dawidzik, J. B., Wallace, J. C., Freund, H. G., Iijima, H. and Budzinski, E. E. Double Base Lesions in DNA X-Irradiated in the Presence or Absence of Oxygen. Previously, double lesions in which two adjacent bases are modified were identified in DNA oligomers exposed in solution to ionizing radiation. However, the formation of such lesions in polymer DNA had not been demonstrated. Using reference oligomer containing a specific double lesion and employing liquid chromatography-mass spectrometry (LC-MS), it was possible to show directly that double lesions are formed in irradiated calf thymus DNA. The double lesion in which a pyrimidine base is degraded to a formamido remnant and an adjacent guanine base is oxidized to 8-oxoguanine was detected in DNA X-irradiated in oxygenated aqueous solution. The double lesion in which the methyl carbon atom of a thymine base is covalently linked to carbon at the 8-position of an adjacent guanine base was detected in DNA irradiated in ...

42 citations

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TL;DR: Irradiation of the dinucleoside monophosphate d(GpT) in an oxygenated solution gives products characterized by damage on one or both guanine and thymine bases, the yields of which were proportional to radiation dose.
Abstract: Irradiation of the dinucleoside monophosphate d(GpT) in an oxygenated solution gives products characterized by damage on one or both guanine and thymine bases, the yields of which were proportional to radiation dose.

41 citations

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TL;DR: The two main cisplatin-induced DNA lesions, G--G and A--G, have been measured in cells exposed to the drug and enzymatically isolated from the DNA in the form of modified dinucleoside monophosphates with the phosphodiester bond intact.

25 citations

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TL;DR: A DNA lesion which results from the breakdown of a pyrimidine base leaving a formamido remnant has been associated with oxidative stress and is shown to be produced in keratinocytes irradiated in culture with UVB light.
Abstract: A DNA lesion which results from the breakdown of a pyrimidine base leaving a formamido remnant has been associated with oxidative stress This lesion is shown to be produced in keratinocytes irradiated in culture with UVB light The amount of formamido lesion produced is comparable to the amount of the 8-hydroxyguanine lesion The two lesions were measured by 32 P-postlabeling and electrochemical detection methods respectively

23 citations


Cited by
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Journal ArticleDOI
TL;DR: The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders, cardiovascular diseases, cardiovascular disease, respiratory diseases, cataract development, rheumatoid arthritis and in various cancers.
Abstract: Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation). Free radicals can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, thereby altering the normal redox status leading to increased oxidative stress. The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders (Parkinson’s disease-PD, Alzheimer’s disease-AD and Multiple sclerosis-MS), cardiovascular diseases (atherosclerosis and hypertension), respiratory diseases (asthma), cataract development, rheumatoid arthritis and in various cancers (colorectal, prostate, breast, lung, bladder cancers). This review deals with chemistry, formation and sources, and molecular targets of free radicals and it provides a brief overview on the pathogenesis of various diseased conditions caused by ROS/RNS.

1,664 citations

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TL;DR: The current status of knowledge and evidence on the mechanisms and involvement of intracellular oxidative stress and DNA damage in human malignancy evolution and possible use of these parameters as cancer biomarkers are presented and controversies related to specific methodologies used for the measurement of oxidatively induced DNA lesions in human cells or tissues are discussed.
Abstract: Cells in tissues and organs are continuously subjected to oxidative stress and free radicals on a daily basis. This free radical attack has exogenous or endogenous (intracellular) origin. The cells withstand and counteract this occurrence by the use of several and different defense mechanisms ranging from free radical scavengers like glutathione (GSH), vitamins C and E and antioxidant enzymes like catalase, superoxide dismutase and various peroxidases to sophisticated and elaborate DNA repair mechanisms. The outcome of this dynamic equilibrium is usually the induction of oxidatively induced DNA damage and a variety of lesions of small to high importance and dangerous for the cell i.e. isolated base lesions or single strand breaks (SSBs) to complex lesions like double strand breaks (DSBs) and other non-DSB oxidatively generated clustered DNA lesions (OCDLs). The accumulation of DNA damage through misrepair or incomplete repair may lead to mutagenesis and consequently transformation particularly if combined with a deficient apoptotic pathway. In this review, we present the current status of knowledge and evidence on the mechanisms and involvement of intracellular oxidative stress and DNA damage in human malignancy evolution and possible use of these parameters as cancer biomarkers. At the same time, we discuss controversies related to potential artifacts inherent to specific methodologies used for the measurement of oxidatively induced DNA lesions in human cells or tissues.

820 citations

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TL;DR: This article focuses on DNA damage on recent aspects of the formation and measurement of oxidatively generated damage in cellular DNA, and recent information concerning the mechanisms of formation, individual measurement, and repair-rate assessment of bipyrimidine photoproducts in isolated cells and human skin upon exposure to UVB radiation, UVA photons, or solar simulated light is critically reviewed.
Abstract: Emphasis has been placed in this article dedicated to DNA damage on recent aspects of the formation and measurement of oxidatively generated damage in cellular DNA in order to provide a comprehensive and updated survey. This includes single pyrimidine and purine base lesions, intrastrand cross-links, purine 5',8-cyclonucleosides, DNA-protein adducts and interstrand cross-links formed by the reactions of either the nucleobases or the 2-deoxyribose moiety with the hydroxyl radical, one-electron oxidants, singlet oxygen, and hypochlorous acid. In addition, recent information concerning the mechanisms of formation, individual measurement, and repair-rate assessment of bipyrimidine photoproducts in isolated cells and human skin upon exposure to UVB radiation, UVA photons, or solar simulated light is critically reviewed.

659 citations

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TL;DR: There is mounting evidence for an important role of freeradical-induced DNA damage in the etiology of numerous diseases including cancer, and understanding of mechanisms of free radical- induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.
Abstract: Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5′-cyclopurine-2′-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importan...

550 citations

Journal ArticleDOI
TL;DR: The aim of this review is to present the structure of all the various known oxidised DNA base lesions known to date and to summarise the present knowledge about the mutagenic and toxic effects of oxidised base modifications and their repair.
Abstract: Oxidative DNA damage is a major cause of cell death and mutagenesis in all aerobic organisms, and several new oxidative base lesions have been identified in recent years. Improved chemistry for the synthesis of oligonucleotides with modified base residues at defined positions has allowed detailed studies of repair, replication, transcription and mutagenesis at specific lesions in vitro and in vivo. The aim of this review is to present the structure of all the various known oxidised DNA base lesions known to date and to summarise the present knowledge about the mutagenic and toxic effects of oxidised base modifications and their repair.

490 citations