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2011 | 58 | 2 | 187-192
Article title

Induction of the multixenobiotic/multidrug resistance system in HeLa cells in response to imidazolium ionic liquids

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The multixenobiotic/multidrug resistance (MXR/MDR) system controls transport of foreign molecules across the plasma membrane as a preventive measure before toxicity becomes apparent. The system consists of an efflux pump, ABCB1, and/or a member of the ABCC family. Ionic liquids are broadly used solvents with several unique properties such as wide liquid range, negligible vapor pressure, good thermal and chemical stability and extraordinary dissolution properties for organic and inorganic compounds. Ionic liquids containing imidazolium ring are frequently used as solvents in drug synthesis. Constitutive and induced amounts of ABCB1 and ABCC1 proteins were estimated here by Western blotting and quantified by flow cytometry in HeLa cells exposed to three homologous 1-alkyl-3-methylimidazolium and one benzyl ring substituted salts. Aliphatic substituents in position 1 of the salts caused a weak toxicity but 1-benzyl ring was strongly toxic. An 8-day long treatment with 10-4 M 1-hexyl-3-methylimidazolium chloride resulted in an about 1.5-fold increase of ABCB1 level and over 2-fold increase of ABCC1 level. The amounts of both investigated ABC-proteins were linearly dependent on the length of the imidazolium ring side chain. Such distinctive changes of the amount of MXR/MDR proteins measured in cultured cells may be a useful marker when screening for potential toxicity of various chemicals.

Physical description
  • Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Gdańsk, Poland
  • Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Gdańsk, Poland
  • Chaudhary PM, Roninson IB (1993) Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J Natl Cancer Inst 85: 632-639.
  • Chin KV, Tanaka S, Darlington G, Pastan I, Gottesman MM (1990) Heat shock and arsenite increase expression of the multidrug resist- ance (MDR1) gene in human renal carcinoma cells. J Biol Chem 265: 221-226.
  • Cole SP, Sparks KE, Fraser K, Loe DW, Grant CE, Wilson GM, Deeley RG (1994) Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 54: 5902-5910.
  • Cordon-Cardo C, O'Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR (1990) Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 38: 1277-1287.
  • Deeley R, Cole S (2006) Substrate recognition and transport by multidrug resistance protein 1 (ABCC1). FEBS Lett 580: 1103-1111.
  • Endicott JA, Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 58: 137-171.
  • Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62: 385-427.
  • Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8: 67-113.
  • Jastorff B, Störmann R, Ranke J, Mölter K, Stock F, Oberheitmann B, Hoffman W, Hoffmann J, Nüchter M, Ondruschka B, Filser J (2003) How hazardous are ionic liquids? Structure-activity relationships and biological testing as important elements for sustainability evaluation. Green Chem 5: 136-142.
  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.
  • Liu FH, Jiang Y (2007) Room temperature ionic liquid as matrix medium for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography. J Chromatogr A 1167: 116-119.
  • Mizuuchi H, Jaitely V, Murdan S, Florence AT (2008) Room temperature ionic liquids and their mixtures: potential pharmaceutical solvents. Eur J Pharm Sci 33: 326-331.
  • Park JG, Kramer BS, Steinberg SM, Carmichael J, Collins JM, Minna JD, Gazdar AF (1987) Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. Cancer Res 47: 5875-5879.
  • Ranke J, Mölter K, Stock F, Bottin-Weber U, Poczobutt J, Hoffmann J, Ondruschka B, Filser J, Jastorff B (2004) Biological effects of imidazolium ionic liquids with varying chain lengths in acute Vibrio fischeri and WST-1 cell viability assays. Ecotoxicol Environ Saf 58: 396-404.
  • Rusiecka I, Składanowski AC (2008) Induction of the multixenobiotic/multidrug resistance system in various cell lines in response to perfluorinated carboxylic acids. Acta Biochim Pol 55: 329-337.
  • Seelig A (1998) A general pattern for substrate recognition by P-glycoprotein. Eur J Biochem 251: 252-261.
  • Składanowski AC, Stepnowski P, Kleszczyński K, Dmochowska B (2005) AMP deaminase in vitro inhibition by xenobiotics. A potential molecular method for risk assessment of synthetic nitro- and polycyclic musks, imidazolium ionic liquids and N-glucopyranosyl ammonium salts. Environ Toxicol Pharmacol 19: 291-296.
  • Stepnowski P, Składanowski AC, Ludwiczak A, Łączyńska E (2004) Evaluating the cytotoxicity of ionic liquids using human cell line HeLa. Hum Exp Toxicol 23: 513-517.
  • Stock F, Hoffmann J, Ranke J, Störmann R, Ondruschka B, Jastorff B (2004) Effects of ionic liquids on the acetylcholinesterase - a structure-activity relationship consideration. Green Chem 6: 286-290.
  • Swatloski RP, Visser AE, Reichert WM, Broker GA, Farina LM, Holbrey JD, Rogers RD (2001) Solvation of 1-butyl-3-imidazolium hexafluorophosphate in aqueous ethanol - a green solution for dissolving hydrophobic ionic liquids. Chem Commun Camb 20: 2070-2071.
  • Swatloski RP, Holbrey JD, Memon SB, Caldwell GA, Rogers RD (2004) Using Caenorhabditis elegans to probe toxicity of 1-alkyl-3-methylimidazolium chloride based ionic liquids. Chem Commun Camb 6: 668-669.
  • Uchiumi T, Kohno K, Tanimura H, Matsuo K, Sato S, Uchida Y, Kuwano M (1993) Enhanced expression of the human multidrug resistance 1 gene in response to UV light irradiation. Cell Growth Differ 4: 147-157.
  • Welton T (1999) Room-temperature ionic liquids. Solvents for synthesis and catalysis. Chem Rev 99: 2071-2083.
  • Zhao D, Liao Y, Zhang Z (2007) Toxicity of ionic liquids. Clean 35: 42-48.
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