Considering the Mechanisms of Cancer Prevention by Selenium

  • Gerald F. CombsJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 492)


Selenium (Se) was recognized as having nutritional importance fairly late in the development of nutrition knowledge (Schwarz and Foltz, 1957) and, for many years, the nature of its role in nutrition remained clouded by the lack of information about its biochemical mechanisms of action. First, it was regarded only as a factor that could somehow “spare” vitamin E in animal diets; and then it became clear that it was specifically required for the synthesis of a number of proteins, including some with antioxidant like functions (glutathione peroxidases [GPX], thioredoxin reductase), as well as others (iodothyronine 5’-deiodinases [DI]) with important metabolic significance of a different type, all of which contained Se in the form of the unusual amino acid, selenocysteine (SeCys). In fact, information about SeCys-proteins continues to emerge and, with it, understanding of the nutritional and health importance of the trace element continues to expand.


Cancer Risk Cancer Prevention Human Skin Fibroblast Syrian Golden Hamster Organoselenium Compound 
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  1. 1.
    Adler, V., Rincus, M. R., Posner, S., Upadhyay, P., El-Bayoumy., K., and Z. Ronai. Effects of chemopreventive selenium compounds on Jun-N-kinase activities. Carcinogenesis 17:1849–1854, 1996.PubMedCrossRefGoogle Scholar
  2. 2.
    An, P. Selenium and endemic cancer in China. In: Environmental bioinorganic chemistry of selenium, edited by P. M. Whanger, G. F. Combs, Jr., and J. Y. Yeh. Beijing: Chin. Acad. Sci. 1995; p. 91–149.Google Scholar
  3. 3.
    Bertling, C. J., Lin, F., and A. W. Girotti. Role of hydrogen peroxide in the cytosolic effects of UCA/B radiation on mammalian cells. Photochem. Photobiol. 64:137–142, 1996.PubMedCrossRefGoogle Scholar
  4. 4.
    Bird, S. M., Uden, P.C., Tyson, J. F., Block, E., and E. Denoyer. Speciation of selenoamino acids and organoselenium compounds in selenium-enriched yeast using high-performace liquid chromatography-inductively coupled plasma mass spectrometry. J. Anal. Atom. Spectrom. 12:785–788, 1997.CrossRefGoogle Scholar
  5. 5.
    Blot, W. J., Li, J. Y., Taylor, P.R., Guo, W., Dawsey, S., Wang, G. Q., Yang. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease specific mortality among adults with esophagal dysplasia. J. Natl. Cancer Inst. 85: 1492–1498, 1993.CrossRefGoogle Scholar
  6. 6.
    Burke, K. E., Combs, Jr., G.F., Gross, E. G., Bhuyan, K. C., and H. Abu-Libdeh. The effects of topical and oral L-selenomethionine on pigmentation and skin cancer induced by ultraviolet irradiation. Nutr. Cancer 17:123–137, 1992.Google Scholar
  7. 7.
    Clark, L. C., Combs, G. F., Jr., Turnbull, B. W., Slate, E., Alberts, D., Abele, D., Allison, R., Bradshaw. The nutritional prevention of cancer with selenium 1983–1993: a randomized clinical trial. J. Am. Med. Assoc. 276:1957–1963, 1996.CrossRefGoogle Scholar
  8. 8.
    Clark, L. C., Dalkin, B., Krongrad, A., Combs, G. F., Jr., Turnbull, B. W., Slate, E. H., Witherington, R., Herlong, J. H., Jansko, E., Carpenter, D., Borosso, C., Falk, S., and J. Rounder. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br. J. Urol. 81:730–734, 1998.PubMedCrossRefGoogle Scholar
  9. 9.
    Clark, L. C., Turnbull, B. W., Slate, E. H., Combs, G. F., Frischbach, L. Subgroup analysis of the nutritional prevention of cancer with selenium trial. Carcinoma of the skin: a randomized trial (unpublished research) 1999.Google Scholar
  10. 10.
    Combs, Jr., G. R. and W. P. Gray. Chemopreventive agents: selenium. Pharmacol. Therapeut. 79:179–192, 1998.CrossRefGoogle Scholar
  11. 11.
    Diamond, A. M., Dale, P., Murray, J. L., and K. J. Grdina. The inhibition of radiation-induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065. Mutat. Res. 356:147–154, 1996.Google Scholar
  12. 12.
    E1-Bayoumy, K., The effects of organoselenium compounds on induction of mouse forestomach tumors by benzo(a)pyrene. Cancer Res. 45:3631–3635, 1985.PubMedGoogle Scholar
  13. 13.
    El-Bayoumy, K., The role of selenium in cancer prevention. In: Practice of oncology, 4thedition. Philadelphia: Lippincott 1991;p. 1–15. DeVita, V. T., Hellman, S., and S. S. Rosenberg (eds.).Google Scholar
  14. 14.
    Emonet, N., Leccia, M. R. Favier, A., Beani, J. C., and M. J. Richard. Thiols and selenium: protective effect of human skin fibroblasts exposed to UVA radiation. J. Photochem. Photobiol. B. 40:84–90, 1997.PubMedCrossRefGoogle Scholar
  15. 15.
    Gray, W. P., Hyun, T., and G. F. Combs, Jr. Low molecular weight selenium in chick plasma. FASEB J. (in press), 1999.Google Scholar
  16. 16.
    Ip, C. Differential effect of dietary methionine on the biopotency of selenomethionine and selenite in cancer chemoprevention. J. Natl. Cancer Inst. 80:258–262, 1988.PubMedCrossRefGoogle Scholar
  17. 17.
    Ip, C. Lessons from basic research in selenium and cancer prevention. J. Nutr. 128:1845–1854, 1998.PubMedGoogle Scholar
  18. 18.
    Ip, C., El-Bayoumy, K., Upadhyaya, P., Ganther, H., Vandanavikit, S., and H. Thompson. Comparative effect on inorganic and organic selenocyanate derivatives in mammary cancer prevention. Carcinogen. 15:187–192, 1994.CrossRefGoogle Scholar
  19. 19.
    Ip, C., and H. Ganther. Activity of methylated forms of selenium in cancer prevention. Cancer Res. 50:1206–1211, 1990.PubMedGoogle Scholar
  20. 20.
    Ip, C. and H. Ganther. Combination of blocking agents and suppressing agents in cancer prevention. Carcinogenesis 12:365, 1991.PubMedCrossRefGoogle Scholar
  21. 21.
    Ip, C. and H. E. Ganther. Comparison of selenium and sulfur analogs in cancer prevention. Carcinogenesis 13:1167–1170, 1992a.CrossRefGoogle Scholar
  22. 22.
    Ip, C. and H. E. Ganther. Biological activities of trimethylselenonium as influenced by arsenite. J. Inorgan. Biochem. 46:215–222, 1992.CrossRefGoogle Scholar
  23. 23.
    Ip, C. and H. Ganther. Novel strategies in selenium cancer chemoprevention research. In: Selenium in biology and human health, edited by R. F. Burk. New York: Springer-Verlag 1993;p. 170–170.Google Scholar
  24. 24.
    Kise, Y., Yamamura, M., Kogata, M., Nakagawa, M., Uetsuji, S., Takada, H., Hioki, K., and M. Yamamoto. Inhibition by selenium of intrahepatic cholangiocarcioma induction in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine. Nutr. Cancer 16: 153–164, 1991.PubMedCrossRefGoogle Scholar
  25. 25.
    Kramer, K., Looks, M. P. Chrissafidou, A., Karsten, S., and J. Areads. Selen and tumarerkrankugen. Akt. Ernahr.-Med. 21:103–113. 1996.Google Scholar
  26. 26.
    Leccia, M. T., Richard, M. J., Beani, J. C., Faure, H., Monjo, A. M., Cadet, J., Amblard, P., and A. Favier. Protective effect of selenium and zinc on UV - A damage in human skin fibroblasts. Photochem. Photobiol. 58:548–553, 1993.CrossRefGoogle Scholar
  27. 27.
    Li, J. Y., Taylor, P.R., Li, B., Blot, Wl J., Guo, W., Dawset, S., Wang, G. Q., Yang, C. S., Zheng, S. F., Gail, M., Li, G. Y., Liu, B. Q., Tangrea, I., Sun, Y. H., Liu, F., Fraumeni, F., Jr., and Y. H., Zhang. Nutrition intervention trials in Linxian, China. J. Nat. Cancer Inst. 85:1492–1498, 1993.CrossRefGoogle Scholar
  28. 28.
    Lu, J., Jiang, C., Kaeck, M., Ganther, H. Ip, C., and H. Thompson. Cellular and metabolic effects of triphenyselenoium chloride in a mammary cell culturer model.Carcinogenesis. 16:513–516, 1995.PubMedCrossRefGoogle Scholar
  29. 29.
    Moysan, A.Jr, Morliere, P., MarquisI. Richard, A., and L. Dubertret. Effects of selenium on UCA-induced lipid peroxidation in cultured human skin fibroblasts. Skin Pharmacol. 8:139–148, 1995.PubMedCrossRefGoogle Scholar
  30. 30.
    Nayini, J., El-Bayoumy, K., Sugie, S., Cohen, L. A., and B. S. Reddy. Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselnocyanate, in rats. Carcinogenesis. 10:509–512, 1989.PubMedCrossRefGoogle Scholar
  31. 31.
    Pence, B. C., Pelier, E., and D. M. Dunn. Effects of dietary selenium UCB-induced skin carcinogenesis and epidermal antioxidant status. J. Invest. Dermatol. 102:759–761, 1994.PubMedCrossRefGoogle Scholar
  32. 32.
    Perchellet, J. P., Abney, N.L. Thomas, R. M., Guislan, Y. L., and E. M., Perchellet. Effects of combined treatments with selenium, glutathione and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction and complete and multistage carcinogenesis in mouse skin. Cancer Res. 47:477–485, 1987.PubMedGoogle Scholar
  33. 33.
    Poirier, K. A., and J. A. Milner, Factors influencing the antitumorigenic properties of selenium in mice. J. Nutr. 113:2147–2154, 1983.PubMedGoogle Scholar
  34. 34.
    Prokopczyk, B., CoxJ. E., UpadhyayaP. Amin, S., DesaiD. HoffmannD. and K. El-Bayoumy. Effects of dietary 1, 4-phenylenebis(methylene)selenocyanate on 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation in lung and liver of A/J mice and F344 rats. Carcinogenesis 17: 749–753, 1996.PubMedCrossRefGoogle Scholar
  35. 35.
    Reddy, B. S., Sugie, S.MaruyamaH. El-Bayoumy, K.and P. Marra. Chemoprevention of colon carcinogenesis by dietary organselenium, benzylselenocyanate, in F344 rats. Cancer Res. 47:5901–5904, 1987.PubMedGoogle Scholar
  36. 36.
    Ronai, Z., Tillotson, J. K., Traganos, F., Darzynkiewice, Z., Conaway, C. C., Upadhyaya, P., and K. El-Bayoumy. Effects of organic and inorganic selenium compounds on rat mammary tumor cells. Int. J. Cancer 63:428–434, 1995.PubMedCrossRefGoogle Scholar
  37. 37.
    Schwarz, K. C. M. Foltz. Selenium as an integral part of factor 3 agains dietary necrotic liver degeneration. J. Am. Chem. Soc. 79:3292–3293, 1957.CrossRefGoogle Scholar
  38. 38.
    Shamberger, R.J. and D. V. Frost. Possible protective effect of selenium against human cancer. Can. Med. Assoc. J. 100:682–686, 1969.Google Scholar
  39. 39.
    Yang, G. Q., Yin, S., and R. Zhou. Studies of safe maximal daily dietary Se-intake in a seleniferous area in China. 1. Selenium intake and tissue selenium levels of the inhabitants. J. Trace Elem. Electrolytes Heatlh Dis. 3:77–86, 1989.Google Scholar
  40. 40.
    Yu, S. Y., Zhu, Y. J., and W. G. Li. Protective role of selenium against hepatitis B virus and primany level cancer in Qidong. Biol. Trace. Elem. Res. 56:117–124, 1997.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Gerald F. CombsJr.
    • 1
  1. 1.Division of Nutritional Sciences Cornell UniversityNY

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