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    <title>UTas ePrints - Upregulation of Glutathione-Related Genes and Enzyme Activities in Cultured Human Cells by Sublethal Concentrations of Inorganic Arsenic</title>
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<meta content="Inorganic arsenic (iAs), a known human carcinogen, acts as a tumor promoter in part by inducing a rapid burst of reactive oxygen species (ROS) in mammalian cells. This causes oxidative stress and a subsequent increase in the level of cellular glutathione (GSH). Glutathione, a ubiquitous reducing sulfhydryl tripeptide, is involved in ROS detoxification and its increase may be part of an adaptive response to the oxidative stress. Glutathione related enzymes including glutathione reductase (GR) and glutathioneS-transferase (GST) also play key roles in these processes. In this study the regulatory effects of inorganic arsenite (AsIII) on the activities of GSH-related enzymes were investigated in cultured human keratinocytes. Substantial increases in GR enzyme activity and mRNA levels were shown in keratinocytes and other human cell lines after exposure to low, subtoxic, micromolar concentrations of AsIII for 24 h. Upregulation of GSH synthesis paralleled the upregulation of GR as shown by increases in glutamate-cysteine lyase (GCL) enzyme activity and mRNA levels, cystine uptake, and intracellular GSH levels. Glutathione S-transferase activity was also shown to increase slightly in keratinocytes, but not in fibroblasts or breast tumor cells. Overall the results show that sublethal arsenic induces a multicomponent response in human keratinocytes that involves upregulation of parts, but not all of the GSH system and counteracts the acute toxic effects of iAs. The upregulation of GR has not previously been shown to be an integral part of this response, although GR is critical for maintaining levels of reduced GSH. " name="eprints.abstract" />
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<meta content="Allen, R. G., and Tresini, M. (2000). Oxidative stress and gene regulation. Free Radical Biol. Med. 28, 463–499.[ISI][Medline]

Anderson, M. E. (1998). Glutathione: An overview of biosynthesis and modulation. Chem. Biol. Interact. 111–112, 1–14.

Babich, H., and Borenfreund, E. (1987). Structure activity relationship (SAR) model established in vitro with the neutral red cytotoxicity assay. Toxicol. in Vitro 1, 3–9.

Barchowsky, A., Klei, L. R., Dudek, E. J., Swartz, H. M., and James, P. E. (1999a). Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radical Biol. Med. 27, 1405–1412.[ISI][Medline]

Barchowsky, A., Roussel, R. R., Klei, L. R., James, P. E., Ganju, N., Smith, K. R., and Dudek, E. J. (1999b). Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways. Toxicol. Appl. Pharmacol. 159, 65–75.[ISI][Medline]

Bergelson, S., Pinkus, R., and Daniel, V. (1994). Intracellular glutathione levels regulate Fos/Jun induction and activation of glutathione S-transferase gene expression. Cancer Res. 54, 36–40.[ISI][Medline]

Byrd, D. M., Roegner, M. L., Griffiths, J. C., Lamm, S. H., Grumski, K. S., Wilson, R., and Lai, S. (1996). Carcinogenic risks of inorganic arsenic in perspective. Int. Arch. Occup. Environ. Health 68, 484–494.[ISI][Medline]

Chan, P. C., and Huff, J. (1997). Arsenic carcinogenesis in animals and in humans: Mechanistic, experimental, and epidemiological evidence. Environ. Carcinog. Ecotoxicol. Rev. 15, 83–122.

Chen, C. J., Chuang, Y. C., Lin, T. M., and Wu, H. Y. (1985). Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers. Cancer Res. 45, 5895–5899.[ISI][Medline]

Chen, C. J., Wu, M. M., Lee, S. S., Wang, J. D., Cheng, S. H., and Wu, H. Y. (1988). Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease. Arteriosclerosis 8, 452–460.[Abstract]

Chouchane, S., and Snow, E. T. (2001). In vitro effect of arsenical compounds on glutathione-related enzymes. Chem. Res. Toxicol. 14, 517–522.[ISI][Medline]

Clarke, J. B., Fortes, M. A., Giovanni, A., and Brewster, D. W. (1996). Modification of an enzymatic glutathione assay for the microtiter plate and the determination of glutathione in rat primary cortical cells. Toxicol. Meth. 6, 223–230.

Davies, M. H., Birt, D. F., and Schnell, R. C. (1984). Direct enzymatic assay for reduced and oxidized glutathione. J. Pharmacol. Methods 12, 191–194.[ISI][Medline]

Deaton, M. A., Bowman, P. D., Jones, G. P., and Powanda, M. C. (1990). Stress protein synthesis in human keratinocytes treated with sodium arsenite, phenyldichloroarsine, and nitrogen mustard. Fundam. Appl. Toxicol. 14, 471–476.[ISI][Medline]

Henseleit, U., Rosenbach, T., and Kolde, G. (1996). Induction of apoptosis in human HaCaT keratinocytes. Arch. Dermatol. Res. 288, 676–683.[ISI][Medline]

Hu, Y., Jin, X., and Snow, E. T. (2002). Effect of arsenic on transcription factor AP-1 and NF-kappaB DNA binding activity and related gene expression. Toxicol. Lett. 133, 33–45.[ISI][Medline]

Huang, C., Ma, W. Y., Li, J., Goranson, A., and Dong, Z. (1999). Requirement of Erk, but not JNK, for arsenite-induced cell transformation. J. Biol. Chem. 274, 14595–14601.[Abstract/Free Full Text]

Kitchin, K. T. (2001). Recent advances in arsenic carcinogenesis: Modes of action, animal model systems, and methylated arsenic metabolites. Toxicol. Appl. Pharmacol. 172, 249–261.[ISI][Medline]

Lee, T. C., and Ho, I. C. (1995). Modulation of cellular antioxidant defense activities by sodium arsenite in human fibroblasts. Arch. Toxicol. 69, 498–504.[ISI][Medline]

Lee, T. C., Wei, M. L., Chang, W. J., Ho, I. C., Lo, J. F., Jan, K. Y., and Huang, H. (1989). Elevation of glutathione levels and glutathione S-transferase activity in arsenic-resistant Chinese hamster ovary cells. In Vitro Cell. Dev. Biol. 25, 442–448.[ISI][Medline]

Lin, S., Cullen, W. R., and Thomas, D. J. (1999). Methylarsenicals and arsinothiols are potent inhibitors of mouse liver thioredoxin reductase. Chem. Res. Toxicol. 12, 924–930.[ISI][Medline]

Liu, J., Liu, Y., Goyer, R. A., Achanzar, W., and Waalkes, M. P. (2000). Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oval or injected inorganic arsenicals. Toxicol. Sci. 55, 460–467.[Abstract/Free Full Text]

Liu, S. X., Athar, M., Lippai, I., Waldren, C., and Hei, T. K. (2001). Induction of oxyradicals by arsenic: Implication for mechanism of genotoxicity. Proc. Natl. Acad. Sci. U.S.A. 98, 1643–1648.[Abstract/Free Full Text]

Lusini, L., Tripodi, S. A., Rossi, R., Giannerini, F., Giustarini, D., del Vecchio, M. T., Barbanti, G., Cintorino, M., Tosi, P., and Di Simplicio, P. (2001). Altered glutathione anti-oxidant metabolism during tumor progression in human renal-cell carcinoma. Int. J. Cancer 91, 55–59.[ISI][Medline]

Maiti, S., and Chatterjee, A. K. (2000). Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency. Environ. Toxicol. Pharmacol. 8, 227–235.[Medline]

Matsui, M., Nishigori, C., Toyokuni, S., Takada, J., Akaboshi, M., Ishikawa, M., Imamura, S., and Miyachi, Y. (1999). The role of oxidative DNA damage in human arsenic carcinogenesis: Detection of 8-hydroxy-2’-deoxyguanosine in arsenic-related Bowen’s disease. J. Invest. Dermatol. 113, 26–31.[ISI][Medline]

Mazumder, D. N., Haque, R., Ghosh, N., De, B. K., Santra, A., Chakraborti, D., and Smith, A. H. (2000). Arsenic in drinking water and the prevalence of respiratory effects in West Bengal, India. Int. J. Epidemiol. 29, 1047–1052.[Abstract/Free Full Text]

Morales, A., Miranda, M., Sanchez-Reyes, A., Colell, A., Biete, A., and Fernandez-Checa, J. C. (1998). Transcriptional regulation of the heavy subunit chain of -glutamylcysteine synthetase by ionizing radiation. FEBS Lett. 427, 15–20.[ISI][Medline]

Ochi, T. (1997). Arsenic compound-induced increases in glutathione levels in cultured Chinese hamster V79 cells and mechanisms associated with changes in -glutamylcysteine synthetase activity, cystine uptake and utilization of cysteine. Arch. Toxicol. 71, 730–740.[ISI][Medline]

Ochi, T., Kaise, T., and Oya-Ohta, Y. (1994). Glutathione plays different roles in the induction of the cytotoxic effects of inorganic and organic arsenic compounds in cultured BALB/c 3T3 cells. Experientia 50, 115–120.[ISI][Medline]

Parrish, A. R., Zheng, X. H., Turney, K. D., Younis, H. S., and Gandolfi, A. J. (1999). Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices. Toxicol. Sci. 50, 98–105.[Abstract/Free Full Text]

Perquin, M., Oster, T., Maul, A., Froment, N., Untereiner, M., and Bagrel, D. (2001). The glutathione-related detoxification system is increased in human breast cancer in correlation with clinical and histopathological features. J. Cancer Res. Clin. Oncol. 127, 368–74.[ISI][Medline]

Pinkus, R., Weiner, L., and Daniel, V. (1996). Role of oxidants and antioxidants in the induction of AP-1, NF-kappaB, and glutathione S-transferase gene expression. J. Biol. Chem. 271, 13422–13429.[Abstract/Free Full Text]

Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

Santra, A., Maiti, A., Das, S., Lahiri, S., Charkaborty, S. K., and Mazumder, D. N. (2000). Hepatic damage caused by chronic arsenic toxicity in experimental animals. J. Toxicol. Clin. Toxicol. 38, 395–405.[ISI][Medline]

Shi, M. M., Kugelman, A., Iwamoto, T., Tian, L., and Forman, H. J. (1994). Quinone-induced oxidative stress elevates glutathione and induces -glutamylcysteine synthetase activity in rat lung epithelial L2 cells. J. Biol. Chem. 269, 26512–26517.[Abstract/Free Full Text]

Snow, E., Hu, Y., Yan, C., and Chouchane, S. (1999). Modulation of DNA repair and glutathione levels in human keratinocytes by micromolar arsenite. In Arsenic Exposure and Health Effects: Proceedings of the Third International Conference on Arsenic Exposure and Health Effects, July 12–15, 1998 (W. R. Chappell, C. O. Abernathy, and R. L. Calderon, Eds.), pp. 243–251. Elsevier Science, Oxford, UK.

Snow, E. T., Schuliga, M., Chouchane, S., and Hu, Y. (2001). Sub-toxic arsenite induces a multi-component protective response against oxidative stress in human cells. In Proceedings of 4th International Conference on Arsenic Exposure and Health Effects (W. R. Chappel, C. O. Abernathy, and R. Calderon, Eds.), pp. 265–275. Elsevier Science, San Diego, CA.

Styblo, M., Delnomdedieu, M., and Thomas, D. J. (1996). Mono- and dimethylation of arsenic in rat liver cytosol in vitro. Chem. Biol. Interact. 99, 147–164.[ISI][Medline]

Styblo, M., Lin, S., Del Razo, L., and Thomas, D. (2001). Trivalent methylated arsenicals: Toxic products of the metabolism of inorganic arsenic. In Arsenic Exposure and Health Effects IV (W. R. Chappell, C. O. Abernathy, and R. L. Calderon, Eds.), pp. 325–337. Elsevier Science, London.

Styblo, M., Serves, S. V., Cullen, W. R., and Thomas, D. J. (1997). Comparative inhibition of yeast glutathione reductase by arsenicals and arsenothiols. Chem. Res. Toxicol. 10, 27–33.[ISI][Medline]

Styblo, M., Vega, L., Germolec, D., Luster, M., Maria Del Razo, L., Wang, C., Cullen, W., and Thomas, D. (1999). Metabolism and toxicity of arsenicals in cultured cells. In Arsenic Exposure and Health Effects: Proceedings of the Third International Conference on Arsenic Exposure and Health Effects, July 12–15, 1998 (W. Chappell, C. Abernathy, and R. Calderon, Eds.), pp. 311–323. Elsevier Science, Oxford, U.K.

Tan, M., Li., S., Swaroop, M., Guan, K., Oberley, L. W., and Sun, Y. (1999). Transcriptional activation of the human glutathione peroxidase promoter by p53. J. Biol. Chem. 274, 12061–12066.[Abstract/Free Full Text]

Tchounwou, P. B., Wilson, B. A., Ishaque, A. B., and Schneider, J. (2001). Atrazine potentiation of arsenic trioxide-induced cytotoxicity and gene expression in human liver carcinoma cells (HepG2). Mol. Cell. Biochem. 222, 49–59.[ISI][Medline]

Thomas, D. J., Styblo, M., and Lin, S. (2001). The cellular metabolism and systemic toxicity of arsenic. Toxicol. Appl. Pharmacol. 176, 127–144.[ISI][Medline]

Tian, K., Norris, A., Lin, C. L., and Li, E. (1997). The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry 36, 5669–5676.[Medline]

Tseng, C. H., Chong, C. K., Chen, C. J., and Tai, T. Y. (1996). Dose-response relationship between peripheral vascular disease and ingested inorganic arsenic among residents in blackfoot disease endemic villages in Taiwan. Atherosclerosis 120, 125–133.[ISI][Medline]

Tseng, W. P., Chu, H. M., How, S. W., Fong, J. M., Lin, C. S., and Yeh, S. (1968). Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J. Natl. Cancer Inst. 40, 453–463.[ISI][Medline]

Vallis, K. A., and Wolf, C. R. (1996). Relationship between the adaptive response to oxidants and stable menadione-resistance in Chinese hamster ovary cell lines. Carcinogenesis 17, 649–654.[Abstract/Free Full Text]

Wang, T. S., Kuo, C. F., Jan, K. Y., and Huang, H. (1996). Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. J. Cell. Physiol. 169, 256–268.[ISI][Medline]

Wong, S. S., Tan, K. C., and Goh, C. L. (1998). Cutaneous manifestations of chronic arsenicism: Review of seventeen cases. J. Am. Acad. Dermatol. 38, 179–185.[ISI][Medline]

Yan, C. C., and Huxtable, R. J. (1995). Fluorimetric determination of monobromobimane and o-phthalaldehyde adducts of -glutamylcysteine and glutathione: Application to assay of -glutamylcysteinyl synthetase activity and glutathione concentration in liver. J. Chromatog. B Biomed. Appl. 672, 217–224.[ISI][Medline]

Yu, R. C., Hsu, K. H., Chen, C. J., and Froines, J. R. (2000). Arsenic methylation capacity and skin cancer. Cancer Epidemiol. Biomark. Prev. 9, 1259–1262.[Abstract/Free Full Text]
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    <h1 class="ep_tm_pagetitle">Upregulation of Glutathione-Related Genes and Enzyme Activities in Cultured Human Cells by Sublethal Concentrations of Inorganic Arsenic</h1>
    <p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Schuliga, Michael</span> and <span class="person_name">Chouchane, Salem</span> and <span class="person_name">Snow, Elizabeth T.</span> (2002) <xhtml:em>Upregulation of Glutathione-Related Genes and Enzyme Activities in Cultured Human Cells by Sublethal Concentrations of Inorganic Arsenic.</xhtml:em> Toxicological Sciences, 70 (2). pp. 183-192.</p><p style="margin-bottom: 1em" class="not_ep_block"></p><table style="margin-bottom: 1em" class="not_ep_block"><tr><td valign="top" style="text-align:center"><a href="http://eprints.utas.edu.au/1775/1/Schuliga-2002-ToxSci.pdf"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a></td><td valign="top"><a href="http://eprints.utas.edu.au/1775/1/Schuliga-2002-ToxSci.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />298Kb</td></tr></table><p style="margin-bottom: 1em" class="not_ep_block">Official URL: <a href="http://toxsci.oxfordjournals.org/cgi/content/abstract/70/2/183">http://toxsci.oxfordjournals.org/cgi/content/abstract/70/2/183</a></p><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">Inorganic arsenic (iAs), a known human carcinogen, acts as a tumor promoter in part by inducing a rapid burst of reactive oxygen species (ROS) in mammalian cells. This causes oxidative stress and a subsequent increase in the level of cellular glutathione (GSH). Glutathione, a ubiquitous reducing sulfhydryl tripeptide, is involved in ROS detoxification and its increase may be part of an adaptive response to the oxidative stress. Glutathione related enzymes including glutathione reductase (GR) and glutathioneS-transferase (GST) also play key roles in these processes. In this study the regulatory effects of inorganic arsenite (AsIII) on the activities of GSH-related enzymes were investigated in cultured human keratinocytes. Substantial increases in GR enzyme activity and mRNA levels were shown in keratinocytes and other human cell lines after exposure to low, subtoxic, micromolar concentrations of AsIII for 24 h. Upregulation of GSH synthesis paralleled the upregulation of GR as shown by increases in glutamate-cysteine lyase (GCL) enzyme activity and mRNA levels, cystine uptake, and intracellular GSH levels. Glutathione S-transferase activity was also shown to increase slightly in keratinocytes, but not in fibroblasts or breast tumor cells. Overall the results show that sublethal arsenic induces a multicomponent response in human keratinocytes that involves upregulation of parts, but not all of the GSH system and counteracts the acute toxic effects of iAs. The upregulation of GR has not previously been shown to be an integral part of this response, although GR is critical for maintaining levels of reduced GSH. </p></div><table style="margin-bottom: 1em" cellpadding="3" class="not_ep_block" border="0"><tr><th valign="top" class="ep_row">Item Type:</th><td valign="top" class="ep_row">Article</td></tr><tr><th valign="top" class="ep_row">Additional Information:</th><td valign="top" class="ep_row">The definitive publisher-authenticated version of Schuliga, Michael and Chouchane, Salem and Snow, Elizabeth T. (2002) Upregulation of Glutathione-Related Genes and Enzyme Activities in Cultured Human Cells by Sublethal Concentrations of Inorganic Arsenic. Toxicological Sciences, 70 (2). pp. 183-192 is available online at: http://toxsci.oxfordjournals.org/cgi/content/abstract/70/2/183</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">arsenite; glutathione; glutathione reductase; keratinocytes; gene expression</td></tr><tr><th valign="top" class="ep_row">Subjects:</th><td valign="top" class="ep_row"><a href="http://eprints.utas.edu.au/view/subjects/320504.html">320000 Medical and Health Sciences &gt; 320500 Pharmacology and Pharmaceutical Sciences &gt; 320504 Toxicology (incl. Clinical Toxicology)</a></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">1775</td></tr><tr><th valign="top" class="ep_row">Deposited By:</th><td valign="top" class="ep_row"><span class="ep_name_citation"><span class="person_name">Dr Elizabeth T Snow</span></span></td></tr><tr><th valign="top" class="ep_row">Deposited On:</th><td valign="top" class="ep_row">12 Sep 2007</td></tr><tr><th valign="top" class="ep_row">Last Modified:</th><td valign="top" class="ep_row">09 Jan 2008 02:30</td></tr><tr><th valign="top" class="ep_row">ePrint Statistics:</th><td valign="top" class="ep_row"><a target="ePrintStats" href="/es/index.php?action=show_detail_eprint;id=1775;">View statistics for this ePrint</a></td></tr></table><p align="right">Repository Staff Only: <a href="http://eprints.utas.edu.au/cgi/users/home?screen=EPrint::View&amp;eprintid=1775">item control page</a></p>
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