Skip to main content
SpringerLink
Log in

Influence of selenium on glutathione and some associated enzymes in rats with mammary tumor induced by 7,12-Dimethylbenz(a)anthracene

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

A recent finding in epidemiological and laboratory studies suggests that the ratio of selenium to glutathione is lower in breast cancer subjects than its control counterparts. Selenium, an antioxidant and anticarcinogen, can modify the status of glutathione and some associated enzymes by blocking peroxidation of lipids in membranes of cancer subjects. Studies were conducted using female albino rats of Wistar strain bearing mammary tumor induced by 7,12-dimethylbenz(a) anthracene to assess the biological role of selenium on some antioxidant enzymes associated with the maintenance of glutathione status. For induction of mammary tumor, 25 mg DMBA in a 1 ml emulsion of sunflower oil and physiological saline was injected subcutaneously to each rat. One group in each of control and tumor bearing rats, were fed 5 mg sodium selenite/kg diet from the day of tumor induction for 24 weeks. Increase in the reduced glutathione concentration was preceded by significant increase in the oxidized glutathione as well as in the activities of γ-glutamylcysteine synthetase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase by selenium administration in rats bearing tumor. However, selenium administration to rats bearing tumor decreased the activity of γ-glutamyl transpeptidase. These observations clearly demonstrate the influence of dietary selenium supplementation in correcting abnormal changes in glutathione turnover and some associated enzymes in tumor induced rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Halliwell B, Gutteridge JMC, Cross CE: Free radicals, antioxidants, and human disease: Where are we now? J Lab Clin Med 119: 598–620, 1992

    Google Scholar 

  2. Cerutti PA: Prooxidant states and tumor promotion. Science 227: 375–380, 1985

    Google Scholar 

  3. Sun Y: Free radicals, antioxidant enzymes, and carcinogenesis. Free Rad Biol Med 8: 583–599, 1990

    Google Scholar 

  4. Bize IB, Oberley LW, Morris HP: Superoxide dismutase and superoxide radical in Morris Hepatomas. Cancer Res 40: 3686–3693, 1980

    Google Scholar 

  5. Willet WC, Stampfer MJ, Hunter D, Colditz GA: The epidemiology of selenium and human cancer. In: A. Aitio, A. Aro, J. Jarvisalo and H. Vainio (eds). Trace Elements in Health and Disease. Royal Society of Chemistry, Cambridge UK, 1991, pp 141–155

    Google Scholar 

  6. Thangaraju M, Vijayalakshmi T, Sachdanandan P: Effect of tamoxifen on lipid peroxides and antioxidative system in postmenopausal women with breast cancer. Cancer 74: 78–82, 1994

    Google Scholar 

  7. Nayini J, El-Bayoumy K, Sugie S, Cohen LA, Reddy BS: Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselenocyanate in rats. Carcinogenesis 10: 509–512, 1989

    Google Scholar 

  8. Ip C, Hayes C, Ganther HE: Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res 51: 595–600, 1991

    Google Scholar 

  9. Ganther HE: Enzymatic synthesis of dimethyl selenide from selenite in mouse liver extracts. Biochemistry 5: 1089–1098, 1966

    Google Scholar 

  10. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG: Selenium, biochemical role as a component of glutathione peroxidase purification and assay. Science 179: 588–590, 1973

    Google Scholar 

  11. Meister A: New aspects of glutathione biochemistry and transport. Nutr Rev 42: 397–410, 1984

    Google Scholar 

  12. Thompson HJ, Clement IP: Temporal changes in tissue glutathione in response to chemical form, dose, and duration of selenium treatment. Relevance to cancer chemoprevention by selenium. Biol Trace Elem Res 30: 163–173, 1991

    Google Scholar 

  13. Kuchan MJ, Milner JA: Influence of intracellular glutathione on selenite mediated growth inhibition of canine mammary tumor cells. Cancer Res 52: 1691–1095, 1992

    Google Scholar 

  14. Liu J, Zhang B, Milner JA: Dietary selenite modifies glutathione metabolism and 7,12-dimethylbenz(a)anthracene conjugation in rats. J Nutr 124: 172–180, 1994

    Google Scholar 

  15. Arun B, Udayachander N, Meenakshi A: 7,12-dimethylbenz(a) anthracene induced mammary tumor in Wistar rats by ‘Air Pouch Techniques’. A new approach. Cancer Lett 25: 187–194, 1984

    Google Scholar 

  16. Ip C, Yip P, Bernardis LL: Role of prolactin in the promotion of dimethylbenz(a)anthracene induced mammary tumors by dietary fat. Cancer Res 40: 374–378, 1980

    Google Scholar 

  17. Ip C, Sinha DK: Enhancement of mammary tumorigenesis by dietary selenium deficiency in rats with a high polyunsaturated fat intake. Cancer Res 41: 31–34, 1981

    Google Scholar 

  18. Drabkin DL, Austin JH: Spectrophotometric studies, spectrophotometric constants for common haemoglobin derivatives in human, dog, and rabbit blood. J Biol Chem 98: 719–733, 1932

    Google Scholar 

  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with Folinphenol reagent. J Biol Chem 193: 265–275, 1951

    Google Scholar 

  20. Tietze F: Enzymatic method for the quantitative determination of nanogram amounts of total and oxidized glutathione applications to mammalian blood and other tissues. Anal Biochem 27: 502–522, 1969

    Google Scholar 

  21. Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212, 1980

    Google Scholar 

  22. Massey V, Williams CH: On the reaction mechanism of yeast glutathione reductase. J Biol Chem 240: 4470–4480, 1965

    Google Scholar 

  23. Habig WB, Jacoby WH: Assays for differentiation of glutathione Stransferase. Methods Enzymol 77: 398–409, 1981

    Google Scholar 

  24. Sekura R, Meister A: γ-glutamylcysteine synthetase further purification, ‘Half of the sites’ reactivity, subunits, and specificity. J Biol Chem 252: 2599–2605, 1977

    Google Scholar 

  25. Tate SS, Meister A: Interaction of y-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analysis of glutathione. J Biol Chem 249: 7593–7602, 1974

    Google Scholar 

  26. Takata K, Watanabe A: Interconvertible microheterogeneity glucose-6 phosphate dehydrogenase in rat liver. Biochem Biophys Acta 235: 19–26, 1971

    Google Scholar 

  27. Snedecor GW, Cochran WG: Statistical Methods. Iowa State University Press, Ames, IA, 1967, pp 272–275

    Google Scholar 

  28. Ames BN: Dietary carcinogens and anticarcinogens. Science 221: 1256–1264, 1983

    Google Scholar 

  29. Liu J, Milner JA: Age, dietary selenium and quanitity of 7,12-dimethylbenz (a) anthracene influence the in vivo occurrence of rat mammary DNA adducts. J Nutr 122: 1361–1368, 1992

    Google Scholar 

  30. Copeland ES: A national institute of health workshop report: Free radicals in promotion — a chemical pathway study section workshop. Cancer Res 43: 5631–5637, 1983

    Google Scholar 

  31. Halliwell B, Gutteridge MC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219: 1–14, 1984

    Google Scholar 

  32. Meister A: Glutathione metabolism and its selective modification. J Biol Chem 263: 17025–17208, 1988

    Google Scholar 

  33. Reed DJ: Regulation of reductive processes by glutathione. Biochem Pharmacol 35: 7–13, 1986

    Google Scholar 

  34. Chidambaram N, Baradarajan A: Dietary selenium effects on lipid peroxidation and glutathione peroxidase in rats with mammary tumour induced by 7,12-dimethylbenz(a)anthracene. Med Sci Res 22: 285–287, 1994

    Google Scholar 

  35. Chidambaram N, Baradarajan A: The effects of selenium on the antioxidative enzymes in rats with mammary tumor induced by 7,12-dimethylbenz(a)anthracene. J Clin Biochem Nutr 18: 89–95, 1995

    Google Scholar 

  36. Yagi K: Lipid peroxides and human diseases. Chem Phys Lipids 45: 337–351, 1987

    Google Scholar 

  37. Levy HR, Christoff M: A critical appraisal of the effect of oxidized glutathione on hepatic glucose 6-phosphate dehydrogenase activity. Biochem J 214: 959–965, 1983

    Google Scholar 

  38. Lopez-Barea J, Lee CY. Mouse liver glutathione reductase purification, kinetics and regulation. Eur J Biochem 98: 487–499, 1979

    Google Scholar 

  39. Liu J, Gilbert K, Parker HM, Haschek WM, Milner JA: Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary tumors and DNA adducts by dietary sclenite. Cancer Res 51: 4613–4617, 1991

    Google Scholar 

  40. El-Bayoumy K, Chae YH, Upadhyaya P, Meschter C, Cohen LA, Reddy BS: Inhibition of 7,12-dimethylbenz(a)anthracene-induced tumors and DNA adduct formation in the mammary glands of female Sprague-Dawlay rats by the synthetic organoselenium compound l,4phenylenebis(methylene)selenocyanate. Cancer Res 52: 2402–2407, 1992

    Google Scholar 

  41. LeBoeuf RA, Laishes BA, Hoekstra WG: Effects of dietary selenium concentration on the development of enzyme-altered liver foci and hepatocellular carcinoma induced by diethylnitrosamine or N acetylaminotluorine in rats. Cancer Res 45: 5489–5495, 1985

    Google Scholar 

  42. Cook JR, Huang DP, Burkhardt AL, Goldman ME, Carroll M, Bresnick E, Chin JF: Assessment of the anti-tumor potential of glutathione. Cancer Lett 21: 277–283, 1984

    Google Scholar 

  43. Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrision PR: The structure of the mouse glutathione peroxidase gene: The selecystein in the active site is encoded by the ‘termination’ codan, TGA. EMBO J 5: 1221–1227, 1986

    Google Scholar 

  44. Reddy AP, Hsu BL, Reddy PS, Li N, Thygaraju K, Reddy CC, Tam MF, To CP: Expression of glutathione peroxide I gene in selenium deficient rats. Nucleic Acids Res 16: 5557–5568, 1988

    Google Scholar 

  45. Yoshimura S, Takekoshi S, Watanabe K, Fuji-kuriyama Y. Determination of nucleotide sequence of cDNA coding rat glutathione peroxidase and diminished expression of the mRNA in selenium deficient rat liver. Biochem Biophys Res Commun 154: 1024–1028, 1988

    Google Scholar 

  46. Chung AS, Maines MD: Effect of selenium on glutathione metabolism induction of γ-glutamylcysteine synthetase and glutathione reductase in the rat liver. Biochem Pharmacol 30: 3217–3223, 1981

    Google Scholar 

  47. Meister A: On the biochemistry of glutathione. In: Glutathione centennial. Molecular perspectives and chemical implications. Academic Press, New York, 1989, pp. 1–19

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Biosciences and Biotechnology, Indian Institute of Technology, 600 036 TN, Madras, India

    Natesan Chidambaram & Anantharanganathan Baradarajan

Authors
  1. Natesan Chidambaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anantharanganathan Baradarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chidambaram, N., Baradarajan, A. Influence of selenium on glutathione and some associated enzymes in rats with mammary tumor induced by 7,12-Dimethylbenz(a)anthracene. Mol Cell Biochem 156, 101–107 (1996). https://doi.org/10.1007/BF00426331

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00426331

Key words

Search

Navigation