Calcium-dependent nitric oxide production is involved in arsenite-induced micronuclei

Gurr, Jia-Ran; Liu, Fount; Lynn, Shugene; Jan, Kun-Yan

doi:10.1016/s1383-5718(98)00076-x

Cited by 74 publications

(37 citation statements)

References 49 publications

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“…The present results show that treatment with arsenite increases DNA strand breaks, and this is due to oxidative DNA damage, as is evident by its sensitivity to various oxidant modulators and to Fpg, but not to nitric oxide synthase inhibitors. In contrast to the present finding, arsenite has been shown to induce DNA damage 12 and micronuclei 19 through the generation of nitric oxide in Chinese hamster ovary cells. Therefore, it seems that different genotoxic mechanisms are involved with arsenite treatment in different types of cells.…”

Section: Discussioncontrasting

confidence: 99%

“…However, we have previously shown that the increase of dichlorofluorescein fluorescence by treatment with arsenite in Chinese hamster ovary cells is due to the induction of nitric oxide. 19 In this investigation, superoxide was measured by the lucigenin-mediated chemiluminescence method. The elevation of superoxide production by treatment with arsenite was made evident by the observation that an appreciable increase of chemiluminescence was detected only when NADH or NADPH was added to the reaction mixture, and the chemiluminescence in extract from arsenite-treated cells was reduced by superoxide dismutase, Tiron, or diphenylene iodinium, but not by nitric oxide synthase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…With a 4-hour treatment, the extent of DNA strand breaks increased with arsenite concentration (Figure 1), and apparent DNA strand breaks were observed in cells treated with arsenite above 1 mol/L. Because nitric oxide 12,19 and reactive oxygen species 20 were shown to be involved in arsenite genotoxicity, the effects of their modulators on arsenite-induced DNA strand breaks were studied. The results show that nitric oxide synthase inhibitors, N -nitro-L-arginine methyl ester and S-methyl-L-thiocitrulline, had no apparent effects ( Figure 2A).…”

Section: Effects Of Arsenite Treatment On Dna Integritymentioning

confidence: 99%

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NADH Oxidase Activation Is Involved in Arsenite-Induced Oxidative DNA Damage in Human Vascular Smooth Muscle Cells

Lynn

Gurr

Lai

et al. 2000

Circulation Research

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278

137

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Abstract-Arsenic is atherogenic, carcinogenic, and genotoxic. Because atherosclerotic plaque has been considered a benign smooth muscle cell tumor, we have studied the effects of arsenite on DNA integrity of human vascular smooth muscle cells. By using single-cell alkaline electrophoresis, apparent DNA strand breaks were detected in a 4-hour treatment with arsenite at a concentration above 1 mol/L. DNA strand breaks of arsenite-treated cells were increased by Escherichia coli formamidopyrimidine-DNA glycosylase and decreased by diphenylene iodinium, superoxide dismutase, catalase, pyruvate, DMSO, or D-mannitol. Extract from arsenite-treated cells showed increased capacity for producing superoxide when NADH was included in the reaction mixture; however, addition of arsenite to extract from untreated cells did not increase superoxide production. The superoxide-producing ability of arsenite-treated cells was also suppressed by diphenylene iodinium, 4,5-dihydroxy-1,2-benzenedisulfonic acid disodium salt (Tiron), or superoxide dismutase. Superoxide production and DNA strand breaks in arsenite-treated cells were also suppressed by transfecting antisense oligonucleotides of p22phox, an essential component of NADH oxidase. Treatment with arsenite also increased the mRNA level of p22phox. These results suggest that arsenite activates NADH oxidase to produce superoxide, which then causes oxidative DNA damage. The result that arsenite at low concentrations increases oxidant levels and causes oxidative DNA damage in vascular smooth muscle cells may be important in arsenic-induced atherosclerosis. (Circ Res. 2000;86:514-519.)Key Words: arsenite Ⅲ oxidative DNA damage Ⅲ NADH oxidase Ⅲ atherosclerosis A rsenic, an element present in the earth's crust, comes to the surface through mining and utilization of groundwater. Serious contamination by inorganic arsenic occurs through long-term ingestion of high concentrations of arsenic in drinking water. Chronic exposure to arsenic has been related to increased incidences of skin, lung, bladder, liver, and kidney cancers. 1,2 Arsenic exposure is also associated with various vascular disorders, including angiosarcomas, 3 atherosclerotic plaques, 4 and hypertension in humans. 5 The epidemiological evidence for shared risk factors for cancer and atherosclerosis has been reviewed by Hansen. 6 Exposure to carcinogenic environmental agents is associated with an increased risk of atherosclerosis. Therefore, somatic mutation and cell proliferation may play a role in the pathogenesis of atherosclerotic plaques. The predominant cell type in plaques is the vascular smooth muscle cell (VSMC). Proliferation of VSMCs is essential for plaque formation and development. By examining the isoenzymes of glucose-6-phosphate dehydrogenase, human atherosclerotic plaques were shown to be monoclonal in origin. 7 Furthermore, DNA samples from human coronary artery plaques were demonstrated to transform NIH3T3 cells. 8 These observations suggest that atherosclerotic plaques are presumably benign smooth muscle...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Arsenite Treatment On Dna Integritymentioning

confidence: 99%

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NADH Oxidase Activation Is Involved in Arsenite-Induced Oxidative DNA Damage in Human Vascular Smooth Muscle Cells

Lynn

Gurr

Lai

et al. 2000

Circulation Research

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278

137

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“…Arsenic, in the presence of Fe 2+ , by Fenton reaction or Haber-Weiss reaction, is known to cause cellular injury through ROS generation [34,35]. Some of the most prominent toxic effects demonstrated in arsenicexposed cells, such as DNA damage [36,37] and apoptosis [38][39][40], have been traced to the generation of reactive oxygen species (ROS) during oxidative stress caused by arsenite [41][42][43][44][45]. Chronic exposure to low levels of arsenic in rats results in depletion of glutathione and increases oxidized glutathione and lipid peroxidation in the brain [46][47][48].…”

Section: • −mentioning

confidence: 99%

Low levels of arsenite activates nuclear factor‐κB and activator protein‐1 in immortalized mesencephalic cells

Kumar

Manna

Wise

et al. 2005

J Biochem & Molecular Tox

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Degeneration of dopaminergic neurons is one of the major features of Parkinson's disease. Many redox-active metals such as iron and manganese have been implicated in neuronal degeneration characterized by symptoms resembling Parkinson's disease. Even though, arsenic, which is another redox-active metal, has been shown to affect the central monoaminergic systems, but its potential in causing dopaminergic cell degeneration has not been fully known. Hence, the present study was designed to investigate arsenic signaling especially that is mediated by reactive oxygen species and its effect on early transcription factors in dopamine producing mesencephalic cell line 1RB3AN27. These mesencephalic cells were treated with low concentrations of sodium arsenite (0.1, 0.5, 1, 5, and 10 microM) and incubated for different periods of time (0-4 h). Arsenite was cytotoxic at 5 and 10 microM concentrations only after 72-h incubation period. Arsenite, in a dose-dependent manner, induced generation of reactive oxygen species (ROS) and activation of early transcription factors such as nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) as shown by electro mobility shift assay. Incubation of antioxidants, either N-acetyl-L-cysteine (50 microM) or alpha-tocopherol (50 microM) with 1 microM arsenite, suppressed ROS generation. Arsenite at 1 microM concentration was sufficient for maximal activation of NF-kappaB and AP-1 activation. Time kinetics studies showed maximal activation of NF-kappaB by 1 microM concentration of arsenite was seen at 120 min and correlated with complete degradation of Ikappa Balpha at 60 min. Similarly, maximal activation of AP-1 by 1 microM concentration of arsenite occurred at 120 min. N-acetyl-L-cysteine at 50 microM concentration inhibited arsenite-induced NF-kappa B and AP-1. In addition, arsenite was shown to induce phosphorylation of extracellular signal regulated kinase (ERK) 1/2 at concentrations of 1 microM and above. These results suggest that arsenite, at low and subcytoxic concentrations, appears to induce oxidative stress leading to activation of early transcription factors whereas addition of antioxidant inhibited the activation of these factors.

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“…In bovine aortic endothelial cells and Chinese hamster ovary cells, treatment with arsenite increases the production of NO (18,19). In Chinese hamster ovary cells, the arseniteinduced NO production is sensitive to calcium modulators.…”

Section: Arsenite-induced Nitric Oxide Seems To Be Calcium Dependentmentioning

confidence: 99%

Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

Bau

Wang

Chung

et al. 2002

Environ Health Perspect

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Arsenic is recognized to be a nonmutagenic carcinogen because it induces DNA damage only at very high concentrations. However, many more DNA strand breaks could be detected by digesting the DNA of arsenite-treated cells with endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K. By doing so, arsenite could be shown to induce DNA damage in human cells within a pathologically meaningful concentration range. Oxidized guanine products were detected in all arsenite-treated human cells examined. DNA-protein cross-links were also detected in arsenite-treated NB4 and HL60 cells. In human umbilical vein endothelial cells, the induction of oxidized guanine products by arsenite was sensitive to inhibitors of nitric oxide (NO) synthase but not to oxidant modulators, whereas the opposite result was obtained in vascular smooth muscle cells. On the other hand, the arsenite-induced oxidized guanine products and DNA-protein cross-links in NB4 and HL60 cells were sensitive to modulators of calcium, NO synthase, oxidant, and myeloperoxidase. Therefore, although oxidized guanine products were detected in all the human cells treated with arsenite, the pathways could be different in different cell types. Because the sensitivity and the mechanism of arsenic intoxication are cell specific, it is important that target tissues and target cells are used for investigations. It is also important that pathologically or pharmacologically meaningful concentrations of arsenic are used. This is because in most cases we are dealing with the chronic effect rather than acute toxicity.

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Calcium-dependent nitric oxide production is involved in arsenite-induced micronuclei

Cited by 74 publications

References 49 publications

NADH Oxidase Activation Is Involved in Arsenite-Induced Oxidative DNA Damage in Human Vascular Smooth Muscle Cells

NADH Oxidase Activation Is Involved in Arsenite-Induced Oxidative DNA Damage in Human Vascular Smooth Muscle Cells

Low levels of arsenite activates nuclear factor‐κB and activator protein‐1 in immortalized mesencephalic cells

Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite.

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