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Volumn 128, Issue 12, 2011, Pages 2775-2782

The natural chemopreventive phytochemical R-sulforaphane is a far more potent inducer of the carcinogen-detoxifying enzyme systems in rat liver and lung than the S-isomer

Author keywords

chemoprevention; chirality; glucosinolates; isothiocyanates; sulforaphane

Indexed keywords

CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 1B1; GLUTATHIONE TRANSFERASE; GLUTATHIONE TRANSFERASE ALPHA; LACTATE DEHYDROGENASE; SULFORAPHANE;

EID: 79955416779     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.25620     Document Type: Article
Times cited : (58)

References (39)
  • 1
    • 34248547027 scopus 로고    scopus 로고
    • Sulforaphane as a promising molecule for fighting cancer
    • DOI 10.1016/j.mrrev.2006.10.004, PII S1383574206000949
    • Fimognari C, Hrelia P,. Sulforaphane as a promising molecule for fighting cancer. Mut Res 2007; 635: 90-104. (Pubitemid 46756397)
    • (2007) Mutation Research - Reviews in Mutation Research , vol.635 , Issue.2-3 , pp. 90-104
    • Fimognari, C.1    Hrelia, P.2
  • 2
    • 62349106315 scopus 로고    scopus 로고
    • Dietary intake of individual glucosinolates in participants of the EIPC-Heidelberg cohort study
    • Steinbrecher A, Linseisen L,. Dietary intake of individual glucosinolates in participants of the EIPC-Heidelberg cohort study. Ann Nutr Met 2009; 54: 87-96.
    • (2009) Ann Nutr Met , vol.54 , pp. 87-96
    • Steinbrecher, A.1    Linseisen, L.2
  • 3
    • 0032948428 scopus 로고    scopus 로고
    • Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress
    • Getahun SM, Chung F-L,. Conversion of isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiol Biomark Prev 1999; 8: 447-51. (Pubitemid 29230550)
    • (1999) Cancer Epidemiology Biomarkers and Prevention , vol.8 , Issue.5 , pp. 447-451
    • Getahun, S.M.1    Chung, F.-L.2
  • 4
    • 38949204895 scopus 로고    scopus 로고
    • Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat
    • DOI 10.1017/S0007114507824093, PII S0007114507824093
    • Hanlon N, Coldham N, Gielbert A, Kuhnert N, Sauer MJ, King LJ, Ioannides C,. Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in the rat. Brit J Nut 2008; 99: 559-64. (Pubitemid 351223423)
    • (2008) British Journal of Nutrition , vol.99 , Issue.3 , pp. 559-564
    • Hanlon, N.1    Coldham, N.2    Gielbert, A.3    Kuhnert, N.4    Sauer, M.J.5    King, L.J.6    Ioannides, C.7
  • 5
    • 69049120201 scopus 로고    scopus 로고
    • Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane in human volunteers
    • Hanlon N, Coldham N, Gielbert A, Sauer MJ, Ioannides C,. Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane in human volunteers. Cancer Lett 2009; 284: 15-20.
    • (2009) Cancer Lett , vol.284 , pp. 15-20
    • Hanlon, N.1    Coldham, N.2    Gielbert, A.3    Sauer, M.J.4    Ioannides, C.5
  • 6
    • 5144230473 scopus 로고    scopus 로고
    • Cancer-preventive isothiocyanates: Measurement of human exposure and mechanism of action
    • DOI 10.1016/j.mrfmmm.2004.04.017, PII S0027510704002908
    • Zhang Y,. Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mut Res 2004; 555: 173-90. (Pubitemid 39345403)
    • (2004) Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis , vol.555 , Issue.1-2 SPEC. ISS. , pp. 173-190
    • Zhang, Y.1
  • 7
    • 0034525122 scopus 로고    scopus 로고
    • Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate
    • Chung FL, Conaway CC, Rao CV, Reddy BS,. Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis 2000; 21: 2287-91. (Pubitemid 32049237)
    • (2000) Carcinogenesis , vol.21 , Issue.12 , pp. 2287-2291
    • Chung, F.-L.1    Conaway, C.C.2    Rao, C.V.3    Reddy, B.S.4
  • 9
    • 33746239394 scopus 로고    scopus 로고
    • Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts
    • DOI 10.1016/j.canlet.2005.09.012, PII S030438350500861X
    • Dinkova-Kostova AT, Jenkins SN, Fahey JW, Ye L, Wehage SL, Liby KT, Stephenson KK, Wade KL, Talalay P,. Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett 2006; 240: 243-52. (Pubitemid 44093825)
    • (2006) Cancer Letters , vol.240 , Issue.2 , pp. 243-252
    • Dinkova-Kostova, A.T.1    Jenkins, S.N.2    Fahey, J.W.3    Ye, L.4    Wehage, S.L.5    Liby, K.T.6    Stephenson, K.K.7    Wade, K.L.8    Talalay, P.9
  • 11
    • 26444561456 scopus 로고    scopus 로고
    • Modulation of hepatic cytochromes P450 and phase II enzymes by dietary doses of sulforaphane in rats: Implications for its chemopreventive activity
    • DOI 10.1002/ijc.21191
    • Yoxall V, Kentish P, Coldham N, Kuhnert N, Sauer MJ, Ioannides C,. Modulation of hepatic cytochromes P450 and phase II enzymes by dietary doses of sulforaphane in rats: implications for its chemopreventive activity. Int J Cancer 2005; 117: 356-62. (Pubitemid 41429558)
    • (2005) International Journal of Cancer , vol.117 , Issue.3 , pp. 356-362
    • Yoxall, V.1    Kentish, P.2    Coldham, N.3    Kuhnert, N.4    Sauer, M.J.5    Ioannides, C.6
  • 12
    • 53249140296 scopus 로고    scopus 로고
    • Up-regulation of the CYP1 family in rat and human liver by the aliphatic isothiocyanates erucin and sulforaphane
    • Hanlon N, Coldham N, Sauer MJ, Ioannides C,. Up-regulation of the CYP1 family in rat and human liver by the aliphatic isothiocyanates erucin and sulforaphane. Toxicology 2008; 252: 92-8.
    • (2008) Toxicology , vol.252 , pp. 92-98
    • Hanlon, N.1    Coldham, N.2    Sauer, M.J.3    Ioannides, C.4
  • 13
    • 57649184041 scopus 로고    scopus 로고
    • Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane
    • Hanlon N, Coldham N, Sauer MJ, Ioannides C,. Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane. Chem-Biol Inter 2009; 177: 115-20.
    • (2009) Chem-Biol Inter , vol.177 , pp. 115-120
    • Hanlon, N.1    Coldham, N.2    Sauer, M.J.3    Ioannides, C.4
  • 14
    • 68149167105 scopus 로고    scopus 로고
    • The aliphatic isothiocyanates erucin and sulforaphane do not effectively up-regulate NAD(P)H: Quinone oxidoreductase (NQO1) in human liver compared with rat
    • Hanlon N, Poynton CL, Coldham N, Sauer MJ, Ioannides C,. The aliphatic isothiocyanates erucin and sulforaphane do not effectively up-regulate NAD(P)H: quinone oxidoreductase (NQO1) in human liver compared with rat. Mol Nutr Food Res 2009; 53: 836-44.
    • (2009) Mol Nutr Food Res , vol.53 , pp. 836-844
    • Hanlon, N.1    Poynton, C.L.2    Coldham, N.3    Sauer, M.J.4    Ioannides, C.5
  • 15
    • 52649162392 scopus 로고    scopus 로고
    • Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane
    • Hanlon N, Okpara M, Coldham N, Sauer MJ, Ioannides C,. Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane. J Agric Food Chem 2008; 56: 7866-71.
    • (2008) J Agric Food Chem , vol.56 , pp. 7866-7871
    • Hanlon, N.1    Okpara, M.2    Coldham, N.3    Sauer, M.J.4    Ioannides, C.5
  • 16
    • 74949124720 scopus 로고    scopus 로고
    • Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture
    • Wagner AE, Ernst I, Iori R, Desel C, Rimbach G,. Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. Exp Dermatol 2009; 19: 137-44.
    • (2009) Exp Dermatol , vol.19 , pp. 137-144
    • Wagner, A.E.1    Ernst, I.2    Iori, R.3    Desel, C.4    Rimbach, G.5
  • 17
    • 55049121677 scopus 로고    scopus 로고
    • Determination of the absolute configuration of the glucosinolate methyl sulfoxide group reveals a stereospecific biosynthesis of the side chain
    • Vergara F, Wenzler M, Hansen BG, Kliebenstein DK, Halkier BA, Gershenzon J, Schneider B,. Determination of the absolute configuration of the glucosinolate methyl sulfoxide group reveals a stereospecific biosynthesis of the side chain. Phytochemistry 2008; 69: 2737-42.
    • (2008) Phytochemistry , vol.69 , pp. 2737-2742
    • Vergara, F.1    Wenzler, M.2    Hansen, B.G.3    Kliebenstein, D.K.4    Halkier, B.A.5    Gershenzon, J.6    Schneider, B.7
  • 18
    • 0001660594 scopus 로고
    • Optical rotatory dispersion and absolute configuration of dialkyl sulfoxides
    • Mislow K, Greenz M, Laur P, Chisholmz D,. Optical rotatory dispersion and absolute configuration of dialkyl sulfoxides. J Am Chem Soc 1964; 87: 665-6.
    • (1964) J Am Chem Soc , vol.87 , pp. 665-666
    • Mislow, K.1    Greenz, M.2    Laur, P.3    Chisholmz, D.4
  • 19
    • 0025359610 scopus 로고
    • An improved method from the purification of myrosinase and its physicochemical characterization
    • DOI 10.1016/0003-9861(90)90346-Z
    • Pessina A, Thomas RM, Palmieri S, Luisi PL,. An improved method for the purification of myrosinase and its physicochemical characterization. Arch Biochem Biophys 1990; 280: 383-9. (Pubitemid 20221980)
    • (1990) Archives of Biochemistry and Biophysics , vol.280 , Issue.2 , pp. 383-389
    • Pessina, A.1    Thomas, R.M.2    Palmieri, S.3    Luisi, P.L.4
  • 20
    • 0034691291 scopus 로고    scopus 로고
    • Hydrolysis of glucosinolates using nylon-immobilized myrosinase to produce pure bioactive molecules
    • DOI 10.1002/(SICI)1097-0290(20000620)68:6<660::AID-BIT9>3.0.CO;2-L
    • Leoni O, Iori R, Palmieri S,. Hydrolysis of glucosinolates using nylon-immobilized myrosinase to produce pure bioactive molecules. Biotechnol Bioeng 2000; 68: 660-4. (Pubitemid 30341445)
    • (2000) Biotechnology and Bioengineering , vol.68 , Issue.6 , pp. 660-664
    • Leoni, O.1    Iori, R.2    Palmieri, S.3
  • 21
    • 0032973226 scopus 로고    scopus 로고
    • Structural and functional integrity of precision-cut liver slices in xenobiotic metabolism: A comparison of the dynamic organ and multiwell plate culture procedures
    • DOI 10.1080/004982599238786
    • Hashemi E, Dobrota M, Till C, Ioannides C,. Structural and functional integrity of precision-cut liver slices in xenobiotic metabolism: a comparison of the dynamic organ and multiwell plate culture procedures. Xenobiotica 1999; 29: 11-25. (Pubitemid 29050388)
    • (1999) Xenobiotica , vol.29 , Issue.1 , pp. 11-25
    • Hashemi, E.1    Dobrota, M.2    Till, C.3    Ioannides, C.4
  • 22
    • 8444237430 scopus 로고    scopus 로고
    • Metabolic and structural viability of precision-cut rat lung slices in culture
    • DOI 10.1080/00498250400000816
    • Umachandran M, Howarth J, Ioannides C,. Metabolic and structural viability of precision-cut rat and lung slices in culture. Xenobiotica 2004; 34: 771-80. (Pubitemid 39487051)
    • (2004) Xenobiotica , vol.34 , Issue.8 , pp. 771-780
    • Umachandran, M.1    Howarth, J.2    Ioannides, C.3
  • 23
    • 0023930873 scopus 로고
    • Direct measurement of NAD(P)H: Quinone reductase from cells cultured in microtiter wells: A screening assay for anticarcinogenic enzyme inducers
    • Prohaska HJ, Santamaria AB,. Direct measurement of NAD(P)H:quinone reductase from cells cultured in microtiter wells: a screening assay for anticarcinogenic enzyme inducers. Anal Biochem 1988; 169: 328-36. (Pubitemid 18081406)
    • (1988) Analytical Biochemistry , vol.169 , Issue.2 , pp. 328-336
    • Prochaska, H.J.1    Santamaria, A.B.2
  • 24
    • 0016275313 scopus 로고
    • Glutathione S-transferase, the first enzymic step in mercapturic acid formation
    • Habig WH, Pabst MJ, Jakoby WB,. Glutathione S-transferase, the first enzymic step in mercapturic acid formation. J Biol Chem 1974; 249: 7130-39.
    • (1974) J Biol Chem , vol.249 , pp. 7130-7139
    • Habig, W.H.1    Pabst, M.J.2    Jakoby, W.B.3
  • 25
    • 0019740345 scopus 로고
    • Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples
    • Akerboom TPH, Sies H,. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Meth Enzymol 1981; 7: 373-82.
    • (1981) Meth Enzymol , vol.7 , pp. 373-382
    • Akerboom, T.P.H.1    Sies, H.2
  • 26
    • 0017184389 scopus 로고
    • A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding
    • Bradford MM,. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
    • (1976) Anal Biochem , vol.72 , pp. 248-254
    • Bradford, M.M.1
  • 27
    • 0034601232 scopus 로고    scopus 로고
    • Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells bydibenzoylmethane and sulforaphane
    • DOI 10.1016/S0304-3835(00)00412-2, PII S0304383500004122
    • Singletary K, MacDonald C,. Inhibition of benzo[α]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells by dibenzoylmethane and sulforaphane. Cancer Lett 2000; 155: 47-54. (Pubitemid 30256223)
    • (2000) Cancer Letters , vol.155 , Issue.1 , pp. 47-54
    • Singletary, K.1    MacDonald, C.2
  • 28
    • 0346888660 scopus 로고    scopus 로고
    • Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes
    • DOI 10.1093/carcin/bgg157
    • Bacon JR, Williamson G, Garner RC, Lappin G, LangouÃt C, Bao Y,. Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes. Carcinogenesis 2003; 24: 1903-11. (Pubitemid 38008530)
    • (2003) Carcinogenesis , vol.24 , Issue.12 , pp. 1903-1911
    • Bacon, J.R.1    Williamson, G.2    Garner, R.C.3    Lappin, G.4    Langouet, S.5    Bao, Y.6
  • 29
    • 10844224317 scopus 로고    scopus 로고
    • Cytochromes P450 in the bioactivation of chemicals
    • DOI 10.2174/1568026043387188
    • Ioannides C, Lewis DFV, Cytochromes P450 in the bioactivation of chemicals. Curr Topics Medicin Chem 2004; 4: 1767-88. (Pubitemid 39662666)
    • (2004) Current Topics in Medicinal Chemistry , vol.4 , Issue.16 , pp. 1767-1788
    • Ioannides, C.1    Lewis, D.F.V.2
  • 30
    • 0028262418 scopus 로고
    • Colorimetric and fluorometric assays of glutathione transferase based on 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole
    • DOI 10.1006/abio.1994.1209
    • Ricci G, Caccuri A, Bello M, Pastore A, Piemont F, Federici G,. Colorimetric and fluorometric assays of glutathione-S-transferase based on 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Anal Biochem 1994; 218: 463-5. (Pubitemid 24141654)
    • (1994) Analytical Biochemistry , vol.218 , Issue.2 , pp. 463-465
    • Ricci, G.1    Caccuri, A.M.2    Lobello, M.3    Pastore, A.4    Piemonte, F.5    Federici, G.6
  • 31
    • 34247606510 scopus 로고    scopus 로고
    • Molecular basis for chemoprevention by sulforaphane: A comprehensive review
    • DOI 10.1007/s00018-007-6484-5
    • Juge N, Mithen RF, Traka M,. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 2007; 64: 1105-27. (Pubitemid 46684547)
    • (2007) Cellular and Molecular Life Sciences , vol.64 , Issue.9 , pp. 1105-1127
    • Juge, N.1    Mithen, R.F.2    Traka, M.3
  • 32
    • 0035987188 scopus 로고    scopus 로고
    • Isothiocyanates as cancer chemopreventive agents: Their biological activities and metabolism in rodents and humans
    • DOI 10.2174/1389200023337496
    • Conaway CC, Yang YM, Chung FL,. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab 2002; 3: 233-55. (Pubitemid 34625038)
    • (2002) Current Drug Metabolism , vol.3 , Issue.3 , pp. 233-255
    • Conaway, C.C.1    Yang, Y.-M.2    Chung, F.-L.3
  • 33
    • 0030273433 scopus 로고    scopus 로고
    • Validation of precision-cut liver slices in dynamic organ culture as an in vitro model for studying CYP1A1 and CYP1A2 induction
    • DOI 10.1006/taap.1996.0236
    • Drahushuk AT, McGarridge BP, Tai H-L, Kitareewan S, Goldstein JA, Olson JR,. Validation of precision-cut liver slices in dynamic organ culture as an in vitro model for studying CYP1A1 and CYP1A2 induction. Toxicol Appl Pharmacol 1996; 140: 393-403. (Pubitemid 26366864)
    • (1996) Toxicology and Applied Pharmacology , vol.140 , Issue.2 , pp. 393-403
    • Drahushuk, A.T.1    McGarrigle, B.P.2    Tai, H.-L.3    Kitareewan, S.4    Goldstein, J.A.5    Olson, J.R.6
  • 34
    • 0030009552 scopus 로고    scopus 로고
    • Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices
    • Lake BG, Charzat C, Tredger JM, Renwick AB, Beamand JA, Price RJ,. Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices. Xenobiotica 1996; 26: 297-306. (Pubitemid 26129016)
    • (1996) Xenobiotica , vol.26 , Issue.3 , pp. 297-306
    • Lake, B.G.1    Charzat, C.2    Tredger, J.M.3    Renwick, A.B.4    Beamand, J.A.5    Price, R.J.6
  • 35
    • 33846844804 scopus 로고    scopus 로고
    • Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities
    • DOI 10.1016/j.tox.2006.11.063, PII S0300483X06007086
    • Pushparajah DS, Umachandran M, Plant KE, Plant N, Ioannides, C,. Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities. Toxicology 2007; 231: 68-80. (Pubitemid 46205035)
    • (2007) Toxicology , vol.231 , Issue.1 , pp. 68-80
    • Pushparajah, D.S.1    Umachandran, M.2    Plant, K.E.3    Plant, N.4    Ioannides, C.5
  • 36
    • 0043166499 scopus 로고    scopus 로고
    • Use of cultured precision-cut rat lung slices to study the in vitro induction of pulmonary cytochrome P450 forms
    • DOI 10.1080/00498225031000108306
    • Lake BG, Meredith C, Scott MP, Renwick AB, Price RJ,. Use of cultured precision-cut rat lung slices to study the in vitro induction of pulmonary cytochrome P450 forms. Xenobiotica 2003; 33: 691-702. (Pubitemid 36966090)
    • (2003) Xenobiotica , vol.33 , Issue.7 , pp. 691-702
    • Lake, B.G.1    Meredith, C.2    Scott, M.P.3    Renwick, A.B.4    Price, R.J.5
  • 37
    • 76749135648 scopus 로고    scopus 로고
    • Modulation of carcinogen-metabolising cytochromes P450 in human liver by the chemopreventive phytochemical phenethyl isothiocyanate, a constituent of cruciferous vegetables
    • Konsue N, Ioannides C,. Modulation of carcinogen-metabolising cytochromes P450 in human liver by the chemopreventive phytochemical phenethyl isothiocyanate, a constituent of cruciferous vegetables. Toxicology 2010; 268: 184-90.
    • (2010) Toxicology , vol.268 , pp. 184-190
    • Konsue, N.1    Ioannides, C.2
  • 38
    • 79952196644 scopus 로고    scopus 로고
    • Differential response of four human livers to modulation of phase II enzyme systems by the chemopreventive phytochemical phenethyl isothiocyanate
    • Konsue N, Ioannides C,. Differential response of four human livers to modulation of phase II enzyme systems by the chemopreventive phytochemical phenethyl isothiocyanate. Mol Nut Food Res 2010; 54: 426-32.
    • (2010) Mol Nut Food Res , vol.54 , pp. 426-432
    • Konsue, N.1    Ioannides, C.2
  • 39
    • 55949121573 scopus 로고    scopus 로고
    • Tissue differences in the modulation of rat cytochromes P450 and phase II conjugation systems by dietary doses of phenethyl isothiocyanate
    • Konsue N, Ioannides C,. Tissue differences in the modulation of rat cytochromes P450 and phase II conjugation systems by dietary doses of phenethyl isothiocyanate. Food Chem Toxicol 2008; 46: 3677-83.
    • (2008) Food Chem Toxicol , vol.46 , pp. 3677-3683
    • Konsue, N.1    Ioannides, C.2


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