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Suppression of sodium arsenite-potentiated cytotoxicity of ultraviolet light by cycloheximide in Chinese hamster ovary cells

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Abstract

Post-treatment with sodium arsenite synergistically increased the cytotoxicity of ultraviolet (UV) light. The potentiation of UV cytotoxicity by sodium arsenite was apparently suppressed by cycloheximide (CHM), a protein synthesis inhibitor. The protective effect of CHM against sodium arsenite-potentiated UV cytotoxicity was well correlated to its activity in inhibiting the synthesis of stress proteins, particularly a small polypeptide with a molecular weight of 8500 dalton. This small stress protein was demonstrated as ubiquitin by immunoprecipitation. Our results also showed that neither ubiquitin induction nor potentiation of UV cytotoxicity by post-treatment with sodium arsenite was observed in the stationary cells. Thus, we suggested that ubiquitin is possibly involved in the action of arsenite in potentiating UV-induced cell killing.

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References

  • Bond U, Agell N, Haas AL, Redman K, Schlesinger MJ (1988) Ubiquitin in stressed chicken embryo fibroblasts. J Biol Chem 263: 2384–2388

    PubMed  Google Scholar 

  • Casto BC, Meyers J, DiPaolo JA (1979) Enhancement of viral transformation for evaluation of the carcinogenic and mutagenic potential of inorganic metal salts. Cancer Res 39: 193–198

    PubMed  Google Scholar 

  • Chu GL, Dewey WC (1987) Effect of cycloheximide on heat-induced cell killing, radiosensitization, and loss of cellular DNA polymerase activities in Chinese hamster ovary cells. Radiat Res 112: 575–580

    PubMed  Google Scholar 

  • Elder PK, Schmidt LJ, Ono T, Getz MJ (1984) Specific stimulation of actin gene transcription by epidermal growth factor and cycloheximide. Proc Natl Acad Sci USA 81: 7476–7480

    PubMed  Google Scholar 

  • Goebl MG, Yochem J, Jentsch S, McGrath JP, Varshavsky A, Byers B (1988) The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science, 241: 1331–1335

    PubMed  Google Scholar 

  • Hershko A (1988) Ubiquitin-mediated protein degradation. J Biol Chem 263: 15237–15240

    PubMed  Google Scholar 

  • Huang RY, Lee TC, Jan KY (1986) Cycloheximide suppresses the enhancing effect of sodium arsenite on the clastogenicity of ethyl methanesulfonate. Mutagenesis 1: 467–470

    PubMed  Google Scholar 

  • IARC (1980) Carcinogenesis of arsenic and arsenic compounds. IARC Monograph on Evaluation of Carcinogenic Risks to Humans 23: 37–141

    Google Scholar 

  • Jan KY, Huang RY, Lee TC (1986) Different modes of action of sodium arsenite, 3-aminobenzamide, and caffeine on the enhancement of ethyl methanesulfonate. Cytogenet Cell Genet 41: 202–208

    PubMed  Google Scholar 

  • Jan KY, Lin YC, Ho IC, Kao SL, Lee TC (1990) Effects of sodium arsenite on the cytotoxicity of bleomycin. Toxicol Lett 51: 81–90

    PubMed  Google Scholar 

  • Jentsch S, McGrath JP, Varshavsky A (1987) The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugation enzyme. Nature 329: 131–134

    PubMed  Google Scholar 

  • Klemperer NS, Pickart CM (1989) Arsenite inhibits two steps in the ubiquitin-dependent proteolytic pathway. J Biol Chem 264: 19245–19252

    PubMed  Google Scholar 

  • Klemperer NS, Berleth ES, Pickart CM (1989) A novel, arsenite-sensitive E2 of the ubiquitin pathway: Purification and properties. Biochemistry 28: 6035–6041

    PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    PubMed  Google Scholar 

  • Lee TC, Huang RY, Jan KY (1985) Sodium arsenite enhances the cytotoxicity, clastogenicity, and 6-thioguanine-resistant mutagenicity of ultraviolet light in Chinese hamster ovary cells. Mutat Res 148: 83–89

    PubMed  Google Scholar 

  • Lee TC, Lee KCC, Tzeng YJ, Huang RY, Jan KY (1986a) Sodium arsenite potentiates the clastogenicity and mutagenicity of DNA crosslinking agents. Environ Mutagen 8: 119–128

    PubMed  Google Scholar 

  • Lee TC, Wuu SW, Huang RY, Lee KCC, Jan KY (1986b) Differential effects of pre- and posttreatment of sodium arsenite on the genotoxicity of methyl methanesulfonate in Chinese hamster ovary cells. Cancer Res 46: 1854–1857

    PubMed  Google Scholar 

  • Leonard A, Lauwerys RR (1980) Carcinogenicity, teratogenicity, and mutagenicity of arsenic. Mutat Res 75: 49–62

    PubMed  Google Scholar 

  • Li GC (1983) Induction of thermotolerance and enhanced heat shock protein synthesis in Chinese hamster fibroblasts by sodium arsenite and ethanol. J Cell Physiol 115: 116–122

    PubMed  Google Scholar 

  • Li JH, Rossman TG (1989) Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis. Mol Toxicol 2: 1–9

    PubMed  Google Scholar 

  • Lindquist S (1986) The heat-shock response. Annu Rev Biochem 55: 1151–1191

    PubMed  Google Scholar 

  • Martin DP, Schmidt RE, DiStefano PS, Lowry OH, Carter JG, Johnson EM Jr (1988) Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 106: 829–944

    PubMed  Google Scholar 

  • Mayer RJ, Doherty F (1986) Intracellular protein catabolism: state of the art. FEBS Lett 198: 181–193

    PubMed  Google Scholar 

  • Okui T, Fujiwara Y (1986) Inhibition of human excision repair by inorganic arsenic and the co-mutagenic effect in V79 Chinese hamster cells. Mutat Res 172: 69–76

    PubMed  Google Scholar 

  • Otani Y, Quinones S, Saus J, Kurkinen M, Harris ED Jr (1990) Cycloheximide induces stromelysin mRNA in cultured human fibroblasts. EurJ Biochem 192: 75–79

    Google Scholar 

  • Rawson C, Cosola-Smith C, Barnes D (1990) Death of serum-free mouse embryo cells caused by epidermal growth factor deprivation is prevented by cycloheximide, 12-o-tetradecanoylphorbol-13-acetate, or vanadate. Exp Cell Res 186: 177–181

    PubMed  Google Scholar 

  • Ringold GM, Dieckmann B, Vannice JL, Trahey M, McCormick F (1984) Inhibition of protein synthesis stimulates the transcription of human β-interferon genes in Chinese hamster ovary cells. Proc Natl Acad Sci USA 81: 3964–3968

    PubMed  Google Scholar 

  • Rossman TG (1981) Enhancement of UV-mutagenesis by low concentration of arsenite inE. coli. Mutat Res 91: 207–211

    PubMed  Google Scholar 

  • Sakai T, Aoike A, Marui N, Kawai K, Nishino H, Fukushima M (1989) Protection by cycloheximide against cytotoxicity induced by vincristine, colchincine, or delta 12-prostaglandin J2 on human osteosarcoma cells. Cancer Res 49: 1193–1196

    PubMed  Google Scholar 

  • Schneider E, Lawson PA, Ralph PK (1989) Inhibition of protein synthesis reduces the cytotoxicity of 4′-(9-acridinylamino)methanesulfonm-anisidide with affecting DNA breakage and DNA topoisomerase II in a murine mastocytoma cell line. Biochem Pharmacol 38: 263–269

    PubMed  Google Scholar 

  • Shirachi DY, Johansen MG, McGowan JP, Tu SH (1983) Tumorigenic effect of sodium arsenite in rat kidney. Proc West Pharmacol Soc 26: 413–415

    PubMed  Google Scholar 

  • Siede W (1988) The RAD6 gene of yeast: a link between DNA repair, chromosome structure and protein degradation? Radiat Environ Biophys 27: 277–286

    PubMed  Google Scholar 

  • Springer TA (1989) Purification of proteins by precipitation. In: Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K (eds) Current protocol in molecular biology, vol 2, section 10.16, Wiley Interscience, New York

    Google Scholar 

  • Sunderman FW (1979) Mechanism of metal carcinogenesis. Biol Trace Elements Res 1: 63–86

    Google Scholar 

  • Wall R, Briskin M, Carter C, Govan H, Taylor A, Kincade P (1986) A labile inhibitor blocks immunoglobulink-light-chain-gene transcription in a pre-B leukemic cell line. Proc Natl Acad Sci USA 83: 295–298

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11 529, Taiwan, Republic of China

    Te-Chang Lee, Shih-Lun Kao & Ling-Huei Yih

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  1. Te-Chang Lee
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  2. Shih-Lun Kao
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  3. Ling-Huei Yih
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Lee, TC., Kao, SL. & Yih, LH. Suppression of sodium arsenite-potentiated cytotoxicity of ultraviolet light by cycloheximide in Chinese hamster ovary cells. Arch Toxicol 65, 640–645 (1991). https://doi.org/10.1007/BF02098029

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  • DOI: https://doi.org/10.1007/BF02098029

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