The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes | British Journal of Nutrition | Cambridge Core (original) (raw)

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

There is a wealth of epidemiological information on antioxidants and their possible prevention of disease progression but very little of the research on antioxidants has involved intervention studies. In this study, the potential protective effect of vitamin C or E supplementation in vivo against endogenous and H2O2-induced DNA damage levels in lymphocytes was assessed. The supplementation involved fourteen healthy male and female non-smokers mean age 25·53 (SD 1·82) years, who were asked to supplement an otherwise unchanged diet with 1000 mg vitamin C daily for 42 d or 800 mg vitamin E daily for 42 d. DNA damage in H2O2-treated peripheral blood lymphocytes (PBL) and untreated PBL before and after supplementation, and during a 6-week washout period was assessed using an ELISA. At each sampling time-point, the red cell concentrate activities of superoxide dismutase, catalase and glutathione peroxidase were also determined. Supplementation with vitamin C or vitamin E decreased significantly H2O2-induced DNA damage in PBL, but had no effect on endogenous levels of DNA damage. The activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were suppressed during the supplementation period. These supplementation regimens may be used to limit the possible adverse effects of reactive oxygen species (including those produced during the course of an immune response) on lymphocytes in vivo, and so help to maintain their functional capacity.

References

Aebi, ABH (1974) Catalase. In Methods in Enzymatic Analysis, vol 2, pp. 643–684 ]Bergmeyer, E, editor]. New York, NY: Academic Press.Google Scholar

Anderson, D, Phillips, BJ, Yu, TW, Ayesh, R and Butterworth, KR (1997) The effects of vitamin C supplementation on biomarkers of oxygen radical generated damage in human volunteers with "low" or "high" cholesterol levels. Environmental and Molecular Mutagenesis 30, 161–274.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed

Barnett, YA and Barnett, CR (1998) DNA damage and mutations: Contributors to the age-related alterations to T-cell mediated immune responses. Mechanisms of Ageing and Development 102, 165–175.CrossRefGoogle Scholar

Barnett, YA and King, CM (1995) An investigation of in vivo antioxidant status, DNA repair capacity and mutation as a function of age in humans. Mutation Research 338, 115–128.CrossRefGoogle ScholarPubMed

Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed

Cheeseman, KH (1993) Lipid peroxidation and cancer. In DNA and Free Radicals pp. 211–228 ]Halliwell, B & Aruoma, OI, editors]. West Sussex: Ellis Horwood Ltd.Google ScholarPubMed

Cole, J, Waugh, APW & Beare, DM (1991) HPRT mutant frequencies in circulating lymphocytes: population studies using normal donors, exposed groups and cancer prone syndromes. In New Horizons in Biological Dosimetry, pp. 319–328 ]Gledhill, BL & Mauro, F, editors]. New York, NY: Wiley–Liss.Google Scholar

Dacie, J & Lewis, SM (1991) Practical Haematology, 7th ed. Edinburgh: Churchill Livingstone U.K. Limited.Google Scholar

Dizdaroglu, M (1993) Chemistry of free radical damage to DNA and nucleoproteins. In DNA and Free Radicals pp. 19–41 ]Halliwell, B & Aruoma, OI, editors]. West Sussex: Ellis Horwood Ltd.Google ScholarPubMed

Duthie, SJ, Ma, A, Ross, MA and Collins, AR (1996) Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Research 56, 1291–1295.Google ScholarPubMed

Fenech, M and Morley, AA (1985) The effect of donor age on spontaneous and induced micronuclei. Mutation Research 148, 99–105.CrossRefGoogle ScholarPubMed

Frei, B (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences, USA 86, 6377–6381.CrossRefGoogle ScholarPubMed

Gregory, SH, Wing, EJ, Hoffman, RA and Simmons, RL (1993) Reactive nitrogen intermediates suppress the primary immunologic response to Listeria. Journal of Immunology 150, 2901–2909.CrossRefGoogle ScholarPubMed

Helliger, F (1980) Ascorbic acid analysis by LCEC. Current Separations (BAS) 2, 4–5.Google Scholar

Jones, DG and Suttle, NF (1981) Some effects of copper deficiency on leucocyte function in sheep and cattle. Research Veterinary Science 31, 151–156.CrossRefGoogle ScholarPubMed

King, CM, Gillespie, ES, McKenna, PG and Barnett, YA (1994) An investigation of mutation as a function of age in humans. Mutation Research 316, 79–90.CrossRefGoogle ScholarPubMed

Ma, L, Hoeijmakers, JHJ and van der Eb, AJ (1995) Mammalian excision repair. Biochimica et Biophysica Acta 124, 137–164.Google Scholar

Meneghini, R & Martins, S (1993) Hydrogen peroxide and DNA damage. In DNA and Free Radicals pp. 211–228 ]Halliwell, B & Aruoma, OI, editors]. West Sussex: Ellis Horwood Ltd.Google Scholar

Metzger, Z, Hoffeld, JT and Oppenheim, JJ (1980) Macrophage-mediated suppression: Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. Journal of Immunology 124, 983–988.CrossRefGoogle ScholarPubMed

Meyer, M, Schreck, R and Baeuerle, PA (1993) H2O2 and antioxidants have opposite effects on activation of NF-κB and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive. The EMBO Journal 12, 2005–2015.CrossRefGoogle ScholarPubMed

Moser, U (1987) Uptake of ascorbic acid by leukocytes. Annals of the New York Academy of Science 201, 215.Google Scholar

Packer, L (1992) Interactions among antioxidants in health and disease: Vitamin E and its redox cycle. Proceedings of Society for Experimental Biology 200, 271–276.CrossRefGoogle ScholarPubMed

Paglia, DE and Valentine, KJA (1967) Characterisation of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Laboratory Medicine 70, 158.Google ScholarPubMed

Pawelec, G, Remarque, E, Barnett, Y and Solana, R (1998) T cells and ageing. Frontiers in Bioscience 3, 39–99.CrossRefGoogle Scholar

Pohl, H and Reidy, JA (1989) Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakages syndromes. Mutation Research 224, 247–252.CrossRefGoogle ScholarPubMed

Schraufstätter, I, Hyslop, PA, Jackson, JH and Cochrane, CG (1988) Oxidant-induced DNA damage of target cells. Journal of Clinical Investigation 82, 1040–1250.CrossRefGoogle ScholarPubMed

Schreck, R, Reiber, P and Baeuerle, PA (1992) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NFκB transcription factor and HIV-1. The EMBO Journal 10, 2247–2258.CrossRefGoogle Scholar

Singh, NP, Danner, DB, Tice, RR, Pearson, JD, Brant, LJ, Morrell, CH and Schneider, EL (1991) Basal DNA damage in individual human lymphocytes with age. Mutation Research 256, 1–6.CrossRefGoogle ScholarPubMed

Strain, JJ, Hannigan, BM and McKenna, PG (1991) The pathophysiology of oxidant damage. Journal of Biomedical Sciences 2, 19–24.Google Scholar

Sweetman, SF, Strain, JJ and McKelvey-Martin, VJ (1997) Effect of antioxidant supplementation on DNA damage and repair in human lymphoblastoid cells. Nutrition and Cancer 27, 122–130.CrossRefGoogle ScholarPubMed

Tates, AD, Van Dam, FJ and Van Mossel, H (1991) Use of the clonal assay for the measurement of frequencies of HPRT mutants in T-lymphocytes from five control populations. Mutation Research 253, 199–213.CrossRefGoogle ScholarPubMed

Thurnham, DI, Smith, E and Flora, PS (1988) Concurrent liquid-chromatographic assay of retinol, α-tocopherol, β-carotene, α-carotene, lycopene and β-cryptoxanthin in plasma, with tocopherol acetate as internal standard. Clinical Chemistry 34, 337–381.CrossRefGoogle ScholarPubMed

Trainor, KJ, Wigmore, DJA, Chrysostomou, J, Dempsey, R, Seshadri, R and Morley, AA (1984) Mutation frequency in human lymphocytes increases with age. Mechanisms of Ageing and Development 27, 83–86.CrossRefGoogle ScholarPubMed

van Loon, AAWM, Groenendijk, RH, Timmerman, AJ, Van der Schans, GP, Lohman, PHM and Baan, RA (1992) Quantitative detection of DNA damage in cells after exposing to ionising radiation by means of an improved immunochemical assay. Mutation Research 274, 19–27.CrossRefGoogle Scholar

Vuilleumieur, JP and Keck, E (1989) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. Journal of Micronutrient Analysis 5, 25–34.Google Scholar

Washko, P, Rotrosen, D and Levine, M (1989) Ascorbic acid transport and accumulation in human neutrophils. Journal of Biological Chemistry 264, 18996–19002.CrossRefGoogle ScholarPubMed