Reduction of Ultraviolet-Induced Immunosuppression and Enhanced Resistance to Ultraviolet-Induced Tumors by Retinyl Palmitate and Canthaxanthin

  • Helen L. Gensler
Part of the Experimental Biology and Medicine book series (EBAM, volume 23)

Abstract

There is strong evidence that UV irradiation is a causal factor in human nonmelanoma skin cancer (1–3), and that immunosuppression is a high risk factor for skin cancer in humans (4,5). The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet irradiation has clearly shown that the genotoxic effect of UV irradiation is only one of the components involved in this process. Immunological factors are also critically important in the pathogenesis of UV induced skin cancers (6,7). Most tumors induced by UV irradiation are highly antigenic and cannot grow in normal syngeneic mice. However, they can grow in immunodepressed or UV irradiated mice. The inability to reject antigenic, syngeneic UV-induced tumors can be transferred from UV irradiated mice to naive recipients with splenocytes bearing an Lyt-1+, Lyt-2, L3T4+, Ia, henotype(8). This anergy has been found to be critical in photocarcinogenesis (9). Significantly, the suppression induced by UV irradiation appears to be restricted to contact hypersensitivity reactions and rejection of tumors induced by UV radiation or some chemicals (10,11). Antibody formation, mitogen reactivity, and allograft rejection are reported to be normal in UV irradiated mice (12–14).

Keywords

Lymphoma Covariance Selenium Carotenoid Hunt 

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References

  1. 1.
    Engel, A., Johnson, M.L. and Haynes, S.G. Health effects of sunlight exposure in the United States. Arch. Dermatol. 124:72–79, 1988.CrossRefGoogle Scholar
  2. 2.
    Forbes, P.D. and Davies, R.E. Photobiology of experimental ultraviolet photocarcinogenesis. In: R.W. Daynes and J.D. Spikes, (eds.), Experimental and Clinical Photoimmunology Vol. 1, pp. 43–60. Boca Raton, Florida: CRC Press, 1986.Google Scholar
  3. 3.
    Kraemer, K.H., Lee, M.M. and Scotto, J. Xeroderma pigmentosum, cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch. Dermatol., 123:241–250, 1987.Google Scholar
  4. 4.
    Sheil, A.G. Cancer after transplantation. World J. Surg. 10:389–396, 1986.CrossRefGoogle Scholar
  5. 5.
    Penn, I. Cancer is a complication of severe immunosuppression. Surg. Gynecol. Obst., 162:603–610, 1986.Google Scholar
  6. 6.
    Kripke, M.L. Immunological unresponsiveness induced by ultraviolet radiation. Immunol. Rev. 80:87–102, 1984.CrossRefGoogle Scholar
  7. 7.
    Daynes, R.A., Bernhard, E.J., Gurish, M.F. and Lynch, D.H. Experimental photoimmunology: Immunologic ramifications of UV-induced carcinogenesis. J. Invest. Dermatol., 77:77–85,1981.CrossRefGoogle Scholar
  8. 8.
    Ullrich, S.E. and Kripke, M.L. Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation. J.immunol., 133:2786–2790, 1984.Google Scholar
  9. 9.
    Fisher, M.S. and Kripke, M.L. Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice. Science, 216:1133–1134, 1982.CrossRefGoogle Scholar
  10. 10.
    Noonan, F.P., Kripke, M.L., Pedersen, G.M., and Greene, M.I. Suppression of contact hypersensitivity in mice by ultraviolet irradiation is associated with defective antigen presentation. Immunology, 43:527–533, 1981.Google Scholar
  11. 11.
    Roberts, L.K., and Daynes, R.A. Modification of the immunogenic properties of chemically induced tumors arising in hosts treated concomitantly with ultraviolet light. J. Immunol. 125:438–447, 1980.Google Scholar
  12. 12.
    Spellman, C.W., Woodward, J.G., and Daynes, R.A. Modification of immunolgical potential by ultraviolet radiation. I. Immune status of short term UV-irradiated mice. Transplantation 24:112–119, 1977.CrossRefGoogle Scholar
  13. 13.
    Kripke, M.L., Lofgreen, J.S., Beard, J., Jessup, JM., and Fisher, M.S. In vivo immune response of mice during carcinogenesis by ultraviolet irradiation. J. Natl. Cancer Inst., 59:1227–1230, 1977.Google Scholar
  14. 14.
    Norbury, K.C., Kripke, M.L., and Budman, M.B. In vitro reactivity of macrophages and lymphocytes from ultraviolet-irradiated mice. J. Natl. Cancer Inst., 59:1231–1235, 1977.Google Scholar
  15. 15.
    Connor, M.J., Lowe, N.J., Breeding, J.H. and Chalet, M. Inhibition of ultraviolet-B skin carcinogenesis by all-trans-retinoic acid regimens that inhibit ornithine decarboxylase induction. Cancer Res., 43:171–174, 1983.Google Scholar
  16. 16.
    Epstein, J.H. and Grekin, D.A. Inhibition of ultraviolet induced carcinogenesis by all-transretinoic acid. J. Invest. Dermatol., 76:178–180, 1981.CrossRefGoogle Scholar
  17. 17.
    Boutwell, R.K., Verma, A.K., Takigawa, M., Loprinzi, C.L. and Carbone, P.P. Retinoids as inhibitors of tumor promotion. In: J.H. Saurat, (ed.) Retinoids: New Trends in Research and Therapy pp. 83–96. Basel, Karger, 1985.Google Scholar
  18. 18.
    Gensler, H.L., Watson, R.R., Moriguchi, S. and Bowden, G.T. Effects of dietary retinyl palmitate or 13-cisretinoic acid on the promotion of tumors in mouse skin. Cancer Res., 47:967–970, 1987.Google Scholar
  19. 19.
    Gensler, H.L., Sim, D.A. and Bowden, G.T. (1986) Influence of the duration of topical 13-cis-retinoi acid treatment on inhibition of mouse skin tumor promotion. Cancer Res., 46:2767–2770, 1986.Google Scholar
  20. 20.
    Malkovsky, M., Hunt, R., Palmer, L., Dore, C. and Medawar, P.B. Retinyl acetate-mediated augmentation of resistance to a transplantable 3-methylcholanthreneinduced fibrosarcoma. Transplantation, 38:158–161, 1984.CrossRefGoogle Scholar
  21. 21.
    Cohen, B.E., Gill, G., Cullen, P.R., and Morris, P.J. Reversal of postoperative immunosuppression in man by vitamin A. Surg. Gynecol. Obstet., 149:658–662, 1979.Google Scholar
  22. 22.
    Fusi, S., Kupper, T.S., Green, JD.R., and Ariyan, S. Reversal of postburn immunosuppression by the administration of vitamin A. Surgery, 96:330–334, 1984.Google Scholar
  23. 23.
    Mathews-Roth, M.M. and Krinsky, N.I. Carotenoid dose level and protection against UV-B induced skin tumors. Photochem. Photobiol. 42:35–38, 1985.CrossRefGoogle Scholar
  24. 24.
    Bendich, A. and Shapiro, S.S. Effect of β- carotene and canthaxanthin on the immune responses of the rat. J. Nutr. 116:2254–2262, 1986.Google Scholar
  25. 25.
    Peng, Y.M., Alberts, D.S., Xu, M.J., Watson, R.R., Gensler, H.L. and Bowden, G.T. Effects of high dietary retinyl palmitate and selenium on tissue distribution of retinoids in mice exposed to tumor initiation and promotion. J. Nutr. Growth Cancer, 3:38–45, 1986.Google Scholar
  26. 26.
    Gensler, H.L. Reduction of immunosuppression in UV-irradiated mice by dietary retinyl palmitate plus canthaxanthin. Carcinogenesis, 10:203–207, 1989.CrossRefGoogle Scholar
  27. 27.
    Dennert, G., Crowley, C., Kouba, J. and Lotan, R. Retinoic acid stimulation of the induction of mouse killer T-cells in allogeneic and syngeneic systems. J. Natl. Cancer Inst., 62:89–94, 1979.Google Scholar
  28. 28.
    Colizzi, V. and Malkovsky, M. Augmentation of interleukin-2 production and delayed hypersensitivity in mice infected with Mycobacterium bovis and fed a diet suppplemented with vitamin A acetate. Infect. Immun., 48:581–583, 1985.Google Scholar
  29. 29.
    Dennert, G. Immunostimulation by retinoic acid. In: J. Nugent, and S. Clark, S. (eds), Retinoids, Differentiation and Disease Ciba Foundation Symposium 113, pp. 117–131. London: Pitman, 1985.Google Scholar
  30. 30.
    Watson, R.R., Moriguchi, S. and Gensler, H.L. Effects of dietary retinyl palmitate and selenium on tumoricidal capacity of macrophages in mice undergoing tumor promotion. Cancer Lett., 36:181–187, 1987.CrossRefGoogle Scholar
  31. 31.
    Krinsky, N.I. and Deneke, S.M. Interaction of oxygen and oxyradicals with carotenoids. J. Natl. Cancer Inst., 69:205–210, 1982.Google Scholar
  32. 32.
    Sprangrude, G.J. and Daynes, R.A. Oxygenated sterols as immunosuppressive agents. In: R.A. Daynes and G. Krueger (eds), Experimental and Clinical Photoimmunology Vol.II, pp. 89–102. Boca Raton, Florida, CRC Press, 1986.Google Scholar
  33. 33.
    Rigby, W.F. The immunobiology of vitamin D. Immunol. Today, 9:54–62, 1988.CrossRefGoogle Scholar
  34. 34.
    Klein, G. Tumor antigens. Annu. Rev. Microbiol. 20:223–252, 1966.CrossRefGoogle Scholar
  35. 35.
    Hellstrom, D.E. and Hellstrom, I. Cellular immunity against tumor antigens. Adv. Cancer Res. 12:167–223, 1969.CrossRefGoogle Scholar
  36. 36.
    Hostetler, L.W., Romerdahl, C.A. and Kripke, M.L. Specificity of antigens on UV radiation-induced antigenic tumor cell variants measured in vitro and in vivo. Cancer Res., 49:1207–1213, 1989.Google Scholar
  37. 37.
    North, R.J. and Dye, E.S. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells. Immunology, 53:47–56, 1985.Google Scholar
  38. 38.
    North, R.J. and Bursuker, I. The generation and decay of the immune response to a progressive fibrosarcoma: Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells. J. Exp. Med., 159:1295–1311, 1984.CrossRefGoogle Scholar
  39. 39.
    Dye, E.S. and North, R.J. Specificity of the T cells that mediate and suppress adoptive immunotherapy of established tumors. J. Leukocyte Biol., 36:27–38, 1984.Google Scholar
  40. 40.
    DiGiacomo, A. and North, R.J. T cell suppressors of antitumor immunity. The production of Ly-1-2+ suppressors of delayed sensitivity precedes the production of suppressors of protective immunity. J. Exp. Med., 164:1179–1192, 1986.CrossRefGoogle Scholar
  41. 41.
    Kripke, M.L., and Fisher, M.S. Immunologic parameters of ultraviolet carcinogenesis. J. Natl. Cancer Inst., 57:211–215, 1976.Google Scholar

Copyright information

© The Humana Press Inc. 1990

Authors and Affiliations

  • Helen L. Gensler
    • 1
  1. 1.Department of Radiation Oncology and Cancer CenterUniversity of Arizona College of MedicineTucsonUSA

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