DNA strand breakage and base modification induced by hydrogen peroxide treatment of human respiratory tract epithelial cells

Spencer, Jeremy P.E.; Jenner, Andrew; Chimel, Ken; Aruoma, Okezie I.; Cross, Carroll E.; Wu, Reen; Halliwell, Barry

doi:10.1016/0014-5793(95)01117-w

Cited by 56 publications

(39 citation statements)

References 28 publications

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“…The induction of DNA strand breaks by exposure of human cells to H 2 O 2 corresponds to a mechanism of oxidative DNA damage [49] and is well correlated with multiple DNA base lesions [50], so we would expect AA to enhance the formation of these lesions too. Other authors have recently reported an enhancing effect of AA on H 2 O 2 -induced formation of 5-hydroxy-2'-deoxycitidine, a product of hydroxyl radical-induced oxidation of 2'-deoxycytidine [51].…”

Section: Discussionmentioning

confidence: 99%

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

Duarte

Jones

2007

Free Radical Biology and Medicine

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Vitamin C (ascorbic acid, AA) is an important antioxidant in human plasma. It is clear, however, that AA has other important, non-antioxidant roles in cells. Of particular interest is its involvement in iron metabolism, since AA enhances dietary iron absorption, increases the activity of Fe 2+ -dependent cellular enzymes, promotes Fenton reactions in vitro and was reported to have deleterious effects in individuals with iron overload. Nevertheless, the ability of AA to modulate iron metabolism and enhance iron-dependent damage in cells, tissues and organisms has not been fully elucidated. Here we investigated the effect of AA on iron-mediated oxidative stress in normal human fibroblasts. Incubation with physiologically relevant concentrations of AA was not harmful but sensitised cells towards H 2 O 2 -induced, iron-dependent DNA strand breakage and cell death. We also report that AA increased the levels of intracellular catalytic iron and concomitantly modulated the expression of two wellestablished iron-regulated genes, ferritin and transferrin receptor. In summary, we present evidence of a novel, non-antioxidant role of AA in human cells, where it increases iron availability and enhances ROS-mediated, iron-dependent damage. We suggest that AA may exacerbate the deleterious effects of metals in vivo and promote normal tissue injury in situations associated with elevated ROS production.

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Section: Discussionmentioning

confidence: 99%

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

Duarte

Jones

2007

Free Radical Biology and Medicine

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“…However, other modifications of guanine or other bases also occur, causing their reduction or ringopening. 68 The consequences of base modifications for mtDNA integrity vary depending on the lesion. For instance, ring fragmentation of bases would block DNA replication.…”

Section: Mtdna As a Target For Ethanol-induced Oxidative Stressmentioning

confidence: 99%

Alcohol and mitochondria: A dysfunctional relationship

2002

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Mitochondria are intimately involved in the generation of and defense against reactive oxygen species (ROS). Mitochondria are themselves targets of oxidative stress and also contribute to mechanisms by which oxidative stress-related signals control cell fate. Ethanol promotes oxidative stress, both by increasing ROS formation and by decreasing cellular defense mechanisms. These effects of ethanol are prominent in the liver, the major site of ethanol metabolism in the body. The question remains to what extent this contributes to ethanol-dependent tissue damage or the susceptibility of cells to other stressors. In this review, we consider how mitochondrial actions of ethanol influence oxidative stress management of liver cells. Mitochondrial electron transport constitutes the major intracellular source of ROS, and ethanol treatment imposes conditions that promote ROS formation by mitochondria, the effects of which may be enhanced by a decrease in mitochondrial oxidative stress defenses. A significant target of ethanol-related increases in oxidative stress is mitochondrial DNA. Ethanol-induced damage to mitochondrial DNA, if not adequately repaired, impairs mitochondrial function, which further increases oxidative stress in the cell, leading to a vicious cycle of accumulating cell damage that is more apparent with advancing age. Uncontrolled mitochondrial formation of ROS promotes the inappropriate activation of the mitochondrial permeability transition, increasing the sensitivity of cells to other proapoptotic or damage signals. In combination with ethanol-induced defects in mitochondrial function, these alterations may promote both apoptotic and necrotic cell death in response to otherwise benign or beneficial challenges and contribute to the onset or progression of alcohol-induced liver diseases.Chronic excessive alcohol consumption causes injury to the liver and other tissues, but, despite intensive study, the factors that relate ethanol intake to the onset and progression of liver disease remain controversial. There is considerable evidence from both human and animal studies that alcohol consumption enhances oxidative stress, in liver as well as in other tissues. However, opinions are divided as to why oxidative stress develops, how it affects liver function, and what its relevance is for liver pathology. 1-6 Mitochondria are recognized as the major intracellular source of reactive oxygen species (ROS), which is generated as a by-product of their major metabolic activity of cellular respiration. 7 Mitochondrial constituents are themselves targets of ROS, and the mitochondrial management of oxidative stress has consequences both for cellular energy metabolism and for the processes that control the onset and progression of the cell death response, whether it results in apoptosis or necrosis. Hence, an understanding of how these complementary functions of mitochondria are affected by alcohol consumption may provide important insights into the mechanisms associated with liver damage. In this review, we wil...

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“…Effect of gas phase cigarette smoke on HBE cell viability. Viability tests were conducted using the Alamar blue assay, which measures mitochondrial metabolic activity, as described in [18,22]. Means are the result of three separate experiments.…”

Section: Lllhourlmentioning

confidence: 99%

DNA damage in human respiratory tract epithelial cells: damage by gas phase cigarette smoke apparently involves attack by reactive nitrogen species in addition to oxygen radicals

et al. 1995

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\bstract Treatment of human respiratory tract tracheobron&al epithelial cells with gas-phase cigarette smoke led to dosedependent DNA strand breakage that was highly correlated with multiple chemical modifications of all four DNA bases. The pattern of base damage suggests attack by hydroxyl radicals (OH'). However, by far the most important base damage in quantitative terms was formation of xanthine and hypoxanthine, presumably resulting from deamination of guanine and adenine respectively. Hence, DNA damage by cigarette smoke may involve reactive riitrogen species as well as reactive oxygen species.

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DNA strand breakage and base modification induced by hydrogen peroxide treatment of human respiratory tract epithelial cells

Cited by 56 publications

References 28 publications

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

Alcohol and mitochondria: A dysfunctional relationship

DNA damage in human respiratory tract epithelial cells: damage by gas phase cigarette smoke apparently involves attack by reactive nitrogen species in addition to oxygen radicals

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