Nitric oxide production by arsenite

Gurr, Jia Ran; Yih, L. H.; Samikkannu, Thangavel; Bau, Da Tian; Lin, Shu Yu; Jan, Kun Yan

doi:10.1016/j.mrfmmm.2003.08.024

Cited by 52 publications

(22 citation statements)

References 109 publications

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“…NO production in response to arsenic has been reported to be increased, decreased or unchanged, depending on the cell-type, the species of arsenical compound, arsenic dose, as well as the detection methods (28,43). Using a highly sensitive electrochemical detection method, we found that under the conditions of this study that NO production was significantly elevated in HaCat cells following treatment with 2 μM As(III) for 24 hrs (Fig.…”

Section: Discussionmentioning

confidence: 55%

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As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimer repair via generation of nitric oxide in human keratinocytes

Ding¹,

Hudson²,

Sun³

et al. 2008

Free Radical Biology and Medicine

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Inorganic arsenic enhances skin tumor formation when combined with other carcinogens including ultraviolet radiation (UVR). The inhibition of DNA damage repair by arsenic has been hypothesized to contribute to the co-carcinogenic activities of arsenic observed in vivo. Cyclobutane pyrimidine dimers (CPDs) are an important mutagenic UVR photoproduct and implicated in the genesis of nonmelanoma skin cancer. The current study demonstrates that low concentrations of arsenite (As(III)) inhibit UVR-induced CPDs repair in a human keratinocyte cell line via nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Following As(III) treatment, NO production and iNOS expression are elevated. Little is known about regulation of iNOS by As(III) and further investigations indicated that p38 mitogen-activated protein kinase (p38 MAPK) and NF-κB are required for As(III) induction of iNOS expression. This As(III)-stimulated signaling cascade was involved in inhibition of UVR-induced CPDs repair as disruption of p38 MAPK activity and NF-κB nuclear translocation counteracted the effects of As(III) on CPD repair. Selective inhibition of iNOS ameliorated As(III) inhibition of CPDs repair thereby suggesting that iNOS is a downstream mediator of As(III) activity. These findings provide evidence that an As(III) stimulated signal transduction cascade culminating in elevated iNOS expression and NO generation is an underlying mechanism for inhibition of UVR-induced DNA damage repair by arsenic.

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Section: Discussionmentioning

confidence: 55%

“…Chronic elevation of NO above normal physiological levels may play a role in initiation, promotion, and progression of some arsenic-related human cancers (28,52). Inhibition of DNA repair processes is one potential mechanism by which As(III) contributes to carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimer repair via generation of nitric oxide in human keratinocytes

Ding¹,

Hudson²,

Sun³

et al. 2008

Free Radical Biology and Medicine

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“…It has been used as biomarker of RNS/ROS damage in the studies of inflammation-related hepatic carcinogenesis 16) . The RNS, such as nitrogen oxide and peroxynitrite (ONOO -), are formed by the reaction between nitric oxide and oxyradicals 17,18) . It was reported that As can induce increase in level of oxyradicals in nervous tissue through inhibiting the activity of superoxide dismutase (SOD) as antioxidant enzyme [19][20][21] .…”

Section: Discussionmentioning

confidence: 99%

Abnormal Expression of 8-Nitroguanine in the Brain of Mice Exposed to Arsenic Subchronically

Piao

et al. 2011

INDUSTRIAL HEALTH

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Arsenic (As) is a well-known carcinogen and a notorious health killer on the earth. The regional As toxicosis is becoming a global problem of public health. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals 1) . Chronic exposure to As resulting in neurotoxicity to nervous system has been receiving more and more attention. The intelligence quotient (IQ) of children in As-rich region was found to be lower than that of children in low As area, and the difference was remarkable 2) . It was shown in animal experiments that As could pass through blood-brain barrier and invade the brain parenchyma, and there was a noticeable correlation between the extent of As exposure and the concentration of As in the brain of guinea pigs and rats 3) . Chaudhuri et al. discovered that even if the As concentration fell into the provisional guideline issued by World Health Organization's (WHO), As could impair the oxidation-reduction equilibrium, enhance the peroxidation level of cephalopin, decrease the glutathione concentration and render the brain tissue vulnerable Abstract: To provide molecular toxicological evidences for exploring the mechanism of arsenicinduced neurotoxicity the accumulation of arsenic (As), the formation of 8-nitroguanine (8-NO 2 -G) were examined in brain tissue of mice exposed to arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1 (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result, the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and 29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l As 2 O 3 , respectively and increased in dose-response manner. Nervous cells in the brain of mice exposed to As showed disappearances of axons, vacuolar degeneration in cytoplasm and karyolysis, whereas no such pathological changes were observed in the control group. Weak immunoreactivity against 8-NO 2 -G was observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More intensive immunoreactivity was found in cells at 4 ppm and it was mainly distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated in the brain of mice exposed to As, but iNOS expression was not disturbed by As exposure. No the 8-NO 2 -G immunoreactivity or abnormal expressions of these genes in brain tissue were observed in controls. These results indicate that As induces high expression of 8-NO 2 -G in brain tissues of mice and that RNA in the cells may be modified by overproduced reactive nitrogen species.

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“…NO levels are also increased in some cells after As III exposure which may contribute to some of the toxic effects of arsenicals via reaction with superoxide to form peroxynitrite [14,40,41]. Because As III -induced genotoxicity can be suppressed by both superoxide dismutase (SOD) and inhibitors of NO synthase in CHO cells, it has been suggested that NO and/or peroxynitrite mediate As III genotoxicity [40,42].…”

Section: Introductionmentioning

confidence: 99%

Genetic Toxicology of Arsenic and Antimony

Rossman¹,

Klein²

2010

Biological Chemistry of Arsenic, Antimony and Bismuth

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Interest in the genetic toxicology of arsenic (As) is motivated by the fact that it is considered as a human carcinogen [1]. The genetic toxicology of arsenicals mainly pertains to that of the trivalent arsenical arsenite (As III ) (Chapter 8) and its trivalent monomethylated and dimethylated metabolites (MMA III and DMA III ) (Chapter 7). The corresponding pentavalent compounds are both less toxic and less genotoxic than the trivalent compounds. This is because the pentavalent compounds are less reactive than the trivalent compounds, which can enter cells more readily than the pentavlent compounds (Chapter 8). Once inside the cell, pentavalent compounds are immediately reduced to trivalent compounds, so the genetic toxicology is attributed to the trivalent species and their products. However, the thioarsenical metabolite dimethyldithioarsinic acid (DMDTA V ), which is pentavalent, shows cytotoxicity and genotoxicty that resembles DMA III rather than DMA V [2]. It must also be kept in mind that some cell lines are able to methylate arsenite. Although hepatocytes are not often used for assessing genotoxicity, rat hepatocytes have a higher rate of methylation than that of human hepatocytes [3]. Insignificant amounts or no methylation was seen in normal human keratinocytes [4], UROtsa cells (SV40-transformed human bladder epithelial line) [3], human lymphoblasts (M. Styblo, personal communication),

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Nitric oxide production by arsenite

Cited by 52 publications

References 109 publications

As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimer repair via generation of nitric oxide in human keratinocytes

As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimer repair via generation of nitric oxide in human keratinocytes

Abnormal Expression of 8-Nitroguanine in the Brain of Mice Exposed to Arsenic Subchronically

Genetic Toxicology of Arsenic and Antimony

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