Arsenite Stimulates Poly(ADP-Ribosylation) by Generation of Nitric Oxide

Lynn, Shugene; Shiung, Jaw-Nan; Gurr, Jia-Ran; Jan, K.Y.

doi:10.1016/s0891-5849(97)00279-7

Cited by 114 publications

(53 citation statements)

References 55 publications

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“…Disruption of the mitochondrial respiratory chain and membrane NADPH oxidase activation by As 2 O 3 have been proposed as sources of superoxide anion (27)(28)(29). It has also been reported that As 2 O 3 is able to increase cellular production of nitrite oxide (30). As illustrated in Fig.…”

Section: Discussionmentioning

confidence: 97%

Arsenic Trioxide Exerts Antitumor Activity through Regulatory T Cell Depletion Mediated by Oxidative Stress in a Murine Model of Colon Cancer

Thomas-Schoemann

Batteux

Mongaret

et al. 2012

The Journal of Immunology

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Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As2O3) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (Treg) numbers. As2O3 induced Treg-selective depletion in vitro. In vivo, tumor-bearing mice injected with 1 mg/kg As2O3 showed a significant decrease in the Treg/CD4 cell ratio and in absolute Treg count versus controls. As2O3 exerted antitumor effects only in immunocompetent mice and enhanced adoptive immunotherapy effects. Inhibition of As2O3-induced Treg depletion by the NO synthase inhibitor NG-nitro-l-arginine methyl ester and the superoxide dismutase mimic manganese [III] tetrakis-(5, 10, 15, 20)-benzoic acid porphyrin suggested that it was mediated by oxidative and nitrosative stress. The differential effect of As2O3 on Treg versus other CD4 cells may be related to differences in the cells’ redox status, as indicated by significant differences in 2′7′dichlorodihydrofluorescein diacetate and 4,5-diaminofluorescein diacetate fluorescence levels. In conclusion, these results show for the first time, to our knowledge, that low doses As2O3 can delay solid tumor growth by depleting Tregs through oxidative and nitrosative bursts, and suggest that As2O3 could be used to enhance the antitumor activity of adoptive immunotherapy strategies in human cancer.

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Section: Discussionmentioning

confidence: 97%

Arsenic Trioxide Exerts Antitumor Activity through Regulatory T Cell Depletion Mediated by Oxidative Stress in a Murine Model of Colon Cancer

Thomas-Schoemann

Batteux

Mongaret

et al. 2012

The Journal of Immunology

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“…Arsenic is known to influence cell division (Debec et al, 1990), and increases chromosomal breaks, sister chromatid exchange and morphological transformation in mammalian cells (Magos et al, 1991). Numerous studies on cultured cell and animal models have shown that arsenic may generate reactive oxygen species to exert its toxicity (Lee-Chen et al, 1993;Cavigelli et al, 1996;Lynn et al, 1998), enhance gene amplification and inhibit DNA repair process . Shibata et al suggested that inorganic arsenic compounds act as cocarcinogens rather than primary carcinogens in vivo as well as in vitro (Shibata et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan

et al. 1999

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SummaryTo understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen's disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinomas (SCC). The result showed that p53 gene mutations were found in 39% of cases with Bowen's disease (9/23), 28.6% of cases with BCC (2/7) and 55.6% of cases with SCC (5/9). Most of the mutation sites were located on exon 5 and exon 8. Moreover, the results from direct sequencing indicated that missense mutations were found at codon 149 (C→T) in one case, codon 175 (G→A) in three cases, codon 273 (G→C) in three cases, codon 292 (T→A) in one case, codon 283 (G→T) in one case, codon 172 (T→C) in one case and codon 284 (C→A) in one case. In addition, silent mutations were also found in four cases. These mutations were located at codons 174, 253, 289 and 298 respectively. In immunohistochemistry analysis, p53 overexpression was found in 43.5% (10/23) of cases with Bowen's disease, 14% (1/7) of cases with BCC and 44% (4/9) of cases with SSC. These findings showed that p53 gene mutation rate in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan is high and that the mutation types are different from those in UV-induced skin cancers.

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“…It was suggested that this process leads to the generation of organic hydroperoxides and oxygen radicals, which, in turn, induce major components of the oxidative stress response, including superoxide dismutase (SOD) and catalase. More recently, arsenic toxicity in eukaryotic cells has also been shown to involve the generation of reactive oxygen intermediates (14,32) or possibly even the formation of nitric oxide (47). Thus, it is likely that arsenic resistance in bacteria and eukaryotic cells involves multiple factors, at least two of which include As(III) efflux pumps and antioxidants.…”

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confidence: 99%

Global Analysis of Cellular Factors and Responses Involved inPseudomonas aeruginosaResistance to Arsenite

et al. 2005

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The impact of arsenite [As(III)] on several levels of cellular metabolism and gene regulation was examined in Pseudomonas aeruginosa. P. aeruginosa isogenic mutants devoid of antioxidant enzymes or defective in various metabolic pathways, DNA repair systems, metal storage proteins, global regulators, or quorum sensing circuitry were examined for their sensitivity to As(III). Mutants lacking the As(III) translocator (ArsB), superoxide dismutase (SOD), catabolite repression control protein (Crc), or glutathione reductase (Gor) were more sensitive to As(III) than wild-type bacteria. The MICs of As(III) under aerobic conditions were 0.2, 0.3, 0.8, and 1.9 mM for arsB, sodA sodB, crc, and gor mutants, respectively, and were 1.5-to 13-fold less than the MIC for the wild-type strain. A two-dimensional gel/matrix-assisted laser desorption ionization-time of flight analysis of As(III)-treated wild-type bacteria showed significantly (>40-fold) increased levels of a heat shock protein (IbpA) and a putative allo-threonine aldolase (GlyI). Smaller increases (up to 3.1-fold) in expression were observed for acetyl-coenzyme A acetyltransferase (AtoB), a probable aldehyde dehydrogenase (KauB), ribosomal protein L25 (RplY), and the probable DNA-binding stress protein (PA0962). In contrast, decreased levels of a heme oxygenase (HemO/PigA) were found upon As(III) treatment. Isogenic mutants were successfully constructed for six of the eight genes encoding the aforementioned proteins. When treated with sublethal concentrations of As(III), each mutant revealed a marginal to significant lag period prior to resumption of apparent normal growth compared to that observed in the wild-type strain. Our results suggest that As(III) exposure results in an oxidative stress-like response in P. aeruginosa, although activities of classic oxidative stress enzymes are not increased. Instead, relief from As(III)-based oxidative stress is accomplished from the collective activities of ArsB, glutathione reductase, and the global regulator Crc. SOD appears to be involved, but its function may be in the protection of superoxide-sensitive sulfhydryl groups.Arsenic is present in numerous disturbed and natural ecosystems and is a top-priority national pollutant. It can exist in multiple oxidation states, with the most common being arsenite [As(III)] and arsenate [As(V)]. As(V) is an analogue of phosphate, and its toxicity is due to the disruption of critical cellular functions or synthesis of essential building blocks. These include uncoupling of ATP phosphorylation that would directly impact energy flow, as well as nucleic acid and phospholipid synthesis. As(III) toxicity is thought to be due predominantly to its ability to covalently bind protein sulfhydryl groups. Of the two species, As(III) is considered the most toxic (16,68).Although some microorganisms can utilize As(V) for anaerobic respiration (81) or oxidize As(III) as a sole energy source (37, 75), arsenic generally is toxic to most microorganisms. Arsenic resistance in bacteria is due, in part,...

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Arsenite Stimulates Poly(ADP-Ribosylation) by Generation of Nitric Oxide

Cited by 114 publications

References 55 publications

Arsenic Trioxide Exerts Antitumor Activity through Regulatory T Cell Depletion Mediated by Oxidative Stress in a Murine Model of Colon Cancer

Arsenic Trioxide Exerts Antitumor Activity through Regulatory T Cell Depletion Mediated by Oxidative Stress in a Murine Model of Colon Cancer

Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan

Global Analysis of Cellular Factors and Responses Involved inPseudomonas aeruginosaResistance to Arsenite

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