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Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study

  • Gitte Ravn-Haren (a1), Britta N. Krath (a1), Kim Overvad (a2), Søren Cold (a3), Sven Moesgaard (a4), Erik H. Larsen (a5) and Lars O. Dragsted (a1)...

Abstract

Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, γ-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71·3 (sd 4·26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 μg, 200 μg or 300 μg Se as Se-enriched yeast (SelenoPrecise®). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

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      Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study
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      Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study
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Corresponding author

*Corresponding author: Dr Gitte Ravn-Haren, fax +45 72347699, email grh@food.dtu.dk

References

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1Clark, LC, Combs, GF Jr, Turnbull, BW, et al. (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276, 19571963.
2Clark, LC, Dalkin, B, Krongrad, A, et al. (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81, 730734.
3Duffield-Lillico, AJ, Slate, EH, Reid, ME, et al. (2003) Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 95, 14771481.
4Duffield-Lillico, AJ, Reid, ME, Turnbull, BW, Combs, GF Jr, Slate, EH, Fischbach, LA, Marshall, JR & Clark, LC (2002) Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev 11, 630639.
5Combs, GF Jr & Gray, WP (1998) Chemopreventive agents: selenium. Pharmacol Ther 79, 179192.
6Whanger, PD (2004) Selenium and its relationship to cancer: an update. Br J Nutr 91, 1128.
7El-Bayoumy, K & Sinha, R (2005) Molecular chemoprevention by selenium: a genomic approach. Mutat Res 591, 224236.
8Rao, L, Puschner, B & Prolla, TA (2001) Gene expression profiling of low selenium status in the mouse intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J Nutr 131, 31753181.
9El-Bayoumy, K, Richie, JP Jr, Boyiri, T, Komninou, D, Prokopczyk, B, Trushin, N, Kleinman, W, Cox, J, Pittman, B & Colosimo, S (2002) Influence of selenium-enriched yeast supplementation on biomarkers of oxidative damage and hormone status in healthy adult males: a clinical pilot study. Cancer Epidemiol Biomarkers Prev 11, 14591465.
10Gipp, JJ, Chang, C & Mulcahy, RT (1992) Cloning and nucleotide sequence of a full-length cDNA for human liver γ-glutamylcysteine synthetase. Biochem Biophys Res Commun 185, 2935.
11Gipp, JJ, Bailey, HH & Mulcahy, RT (1995) Cloning and sequencing of the cDNA for the light subunit of human liver γ-glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues. Biochem Biophys Res Commun 206, 584589.
12Chen, C & Kong, AN (2004) Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med 36, 15051516.
13Yoshioka, K, Deng, T, Cavigelli, M & Karin, M (1995) Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. Proc Natl Acad Sci U S A 92, 49724976.
14Venugopal, R & Jaiswal, AK (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc Natl Acad Sci U S A 93, 1496014965.
15Jardine, H, MacNee, W, Donaldson, K & Rahman, I (2002) Molecular mechanism of transforming growth factor (TGF)-β1-induced glutathione depletion in alveolar epithelial cells. Involvement of AP-1/ARE and Fra-1. J Biol Chem 277, 2115821166.
16Li, Y & Jaiswal, AK (1992) Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element. J Biol Chem 267, 1509715104.
17Mulcahy, RT & Gipp, JJ (1995) Identification of a putative antioxidant response element in the 5′-flanking region of the human γ-glutamylcysteine synthetase heavy subunit gene. Biochem Biophys Res Commun 209, 227233.
18Reiter, R & Wendel, A (1984) Selenium and drug metabolism – II. Independence of glutathione peroxidase and reversibility of hepatic enzyme modulations in deficient mice. Biochem Pharmacol 33, 19231928.
19Mimura, J, Ema, M, Sogawa, K & Fujii-Kuriyama, Y (1999) Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13, 2025.
20Cauchi, S, Stucker, I, Cenee, S, Kremers, P, Beaune, P & Massaad-Massade, L (2003) Structure and polymorphisms of human aryl hydrocarbon receptor repressor (AhRR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer. Pharmacogenetics 13, 339347.
21Rayman, MP (2000) The importance of selenium to human health. Lancet 356, 233241.
22Lyhne, N, Christensen, T, Groth, MV, Fagt, S, Biltoft-Jensen, A, Hartkopp, H, Hinsch, H-J, Matthiessen, J, Møller, A, Saxholt, E & Trolle, E (2005) Danskernes Kostvaner 2000–2002. Hovedresultater (Dietary Habits in Denmark 2000–2002. Main Results). Søborg, Denmark: Danish Institute for Food and Veterinary Research.
23Larsen, EH, Hansen, M, Paulin, H, Moesgaard, S, Reid, M & Rayman, M (2004) Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies. J AOAC Int 87, 225232.
24Sloth, JJ, Larsen, EH, Bugel, SH & Moesgaard, S (2003) Determination of total selenium and Se 77 in isotopically enriched human samples by ICP-dynamic reaction cell-MS. JAAS 18, 317322.
25Wheeler, CR, Salzman, JA, Elsayed, NM, Omaye, ST & Korte, DW Jr (1990) Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Anal Biochem 184, 193199.
26Dragsted, LO, Pedersen, A, Hermetter, A, Basu, S, Hansen, M, Haren, GR, Kall, M, Breinholt, V, Castenmiller, JJ, Stagsted, J, Jacobsen, J, Skibsted, L, Rasmussen, SE, Loft, S & Sandström, B (2004) The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers. Am J Clin Nutr 79, 10601072.
27Alfthan, G, Aro, A, Arvilommi, H & Huttunen, JK (1991) Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate. Am J Clin Nutr 53, 120125.
28Thomson, CD, Robinson, MF, Butler, JA & Whanger, PD (1993) Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women. Br J Nutr 69, 577588.
29Levander, OA, Alfthan, G, Arvilommi, H, Gref, CG, Huttunen, JK, Kataja, M, Koivistoinen, P & Pikkarainen, J (1983) Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters. Am J Clin Nutr 37, 887897.
30Nève, J (1995) Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol 9, 6573.
31Nève, J, Vertongen, F & Capel, P (1988) Selenium supplementation in healthy Belgian adults: response in platelet glutathione peroxidase activity and other blood indices. Am J Clin Nutr 48, 139143.
32Brown, KM, Pickard, K, Nicol, F, Beckett, GJ, Duthie, GG & Arthur, JR (2000) Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphoctyes, granulocytes, platelets and erythrocytes. Clin Sci (Lond) 98, 593599.
33Bukkens, SG, de Vos, N, Kok, FJ, Schouten, EG, de Bruijn, AM & Hofman, A (1990) Selenium status and cardiovascular risk factors in healthy Dutch subjects. J Am Coll Nutr 9, 128135.
34Ravn-Haren, G, Olsen, A, Tjonneland, A, Dragsted, LO, Nexo, BA, Wallin, H, Overvad, K, Raaschou-Nielsen, O & Vogel, U (2006) Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis 27, 820825.
35Tsuchiya, Y, Nakajima, M, Itoh, S, Iwanari, M & Yokoi, T (2003) Expression of aryl hydrocarbon receptor repressor in normal human tissues and inducibility by polycyclic aromatic hydrocarbons in human tumor-derived cell lines. Toxicol Sci 72, 253259.
36Carlsen, H, Myhrstad, MC, Thoresen, M, Moskaug, JO & Blomhoff, R (2003) Berry intake increases the activity of the γ-glutamylcysteine synthetase promoter in transgenic reporter mice. J Nutr 133, 21372140.
37Whitney, AR, Diehn, M, Popper, SJ, Alizadeh, AA, Boldrick, JC, Relman, DA & Brown, PO (2003) Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A 100, 18961901.
38Finnstrom, N, Thorn, M, Loof, L & Rane, A (2001) Independent patterns of cytochrome P450 gene expression in liver and blood in patients with suspected liver disease. Eur J Clin Pharmacol 57, 403409.
39Raucy, JL, Schultz, ED, Wester, MR, Arora, S, Johnston, DE, Omdahl, JL & Carpenter, SP (1997) Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity. Drug Metab Dispos 25, 14291435.

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