Original Article

Journal of Investigative Dermatology (1990) 95, 530–536; doi:10.1111/1523-1747.ep12504877

Susceptibility to Effects of UVB Radiation on Induction of Contact Hypersensitivity as a Risk Factor for Skin Cancer in Humans

Takeshi Yoshikawa1, Virginia Rae2, Warner Bruins-Slot1, Jan-Willem van den Berg1, J Richard Taylor3 and J Wayne Streilein1

  1. 1Departments of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, U.S.A.
  2. 2Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida, U.S.A.
  3. 3Veterans Administration Hospital at Miami, Miami, Florida, U.S.A.

Received 26 April 1990; Accepted 30 June 1990.

Top

Abstract

Normal, healthy human volunteers and patients with proved history of non-melanoma skin cancer have been tested for their capacity to develop contact hypersensitivity to dinitrochlorobenzene (DNCB) following exposure of buttock skin to acute, low-dose ultraviolet B (UVB) radiation. Using a radiation protocol that achieves virtually complete depletion of normal-appearing Langerhans cells from irradiated skin, it was learned that approximately 60% of healthy volunteers developed vigorous contact hypersensitivity (CH) when 2000 mug DNCB was painted on the irradiated site. These individuals were designated UVB-resistant, and were distinguished from other individuals, designated UVB-susceptible, who failed to develop contact hypersensitivity following an identical treatment protocol. It was then discovered that virtually all (92%) skin cancer patients exposed to UVB and DNCB failed to develop CH, i.e., were UVB-susceptible. In subsequent experiments, epicutaneous application of 2000 mug DNCB to unirradiated skin of UVB-susceptible individuals revealed a further distinction between normal persons and skin cancer patients. Approximately 45%ot the latter (and none of the former) remained unresponsive (failed to develop contact hypersensitivity following this second attempt at sensitization), implying that they had been rendered immunologically tolerant. These tolerant individuals responded normally to the unrelated hapten, diphencyprone. We conclude that human beings resemble inbred strains of laboratory mice in that some individuals are UVB- susceptible, whereas others are UVB-resistant. Because the incidence of UVB-susceptibility was significantly higher in skin cancer patients, and as specific unresponsiveness could be demonstrated only in these patients, we propose that UVB- susceptibility, as we define it in this hapten system, may be a risk factor for the development of skin cancer.

Top

References

  1. Scotto, J, Kopf, A. W, Urbach, F: Nonmelanoma skin cancer in four areas of the U.S. Cancer 1974 34: 1331–1338,
  2. Vitaliano, PP, Urbach, F: The relative importance of risk factors in nonmelanoma carcinoma. Arch Dermatol 1980 116: 454–456,  | Article | PubMed | ISI | ChemPort |
  3. Green, AES, Findley, GB, Klenk, KF, Wilsno, WM, Mo, T: The ultraviolet dose dependence of nonmelanoma skin cancer incidence. Photochem Photobiol 1976 24: 353–362,  | PubMed | ChemPort |
  4. Harber, LC, Bickers, DR: Ultraviolet carcinogenesis. In: Photosensitivity Diseases. W. B. Saunders, Philadelphia, 1981, pp 246–257,
  5. Kripke, ML, Lofgreen, JS, Beard, J, Jessup, JM, Fisher, MS: In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation. J Natl Cancer Inst 1977 59: 1227–1241,  | PubMed | ChemPort |
  6. Streilein, JW: Skin Associated Lymphoid Tissues (SALT). J Invest Dermatol 1983 80: 12–16,  | Article | PubMed | ChemPort |
  7. Kripke, ML: Immunobiology of photocarcinogenesis. In: Parrish HA (ed.): The Effect of Ultraviolet Radiation on the Immune System, Johnson and Johnson Products 1983, New Brunswick, NJ, pp 87–106,
  8. Daynes, RA, Schmitt, MK, Roberts, LK, Spellman, CW: Phenotypic and physical characteristics of the lymphoid cells involved in the immunity to syngeneic UV-induced tumors. J Immunol 1979 122: 2458–2464,  | PubMed | ChemPort |
  9. Daynes, RA, Samlowski, WE, Burnham, DK, Gahring, LC, Roberts, LK: Immunobiological consequences of acute and chronic UV exposure. In: Therapeutic Medicine, S. Karger, Basel, 1985
  10. Toews, GB, Bergstresser, PR, Streilein, JW: Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol 1980 124: 445–453,  | PubMed | ISI | ChemPort |
  11. Lynch, DH, Gurish, MF, Daynes, RA: Relationship between epidermal Langerhans cell density, ATPase activity and the induction of contact hypersensitivity. J Immunol 1981 126: 1892–1897,  | PubMed | ISI | ChemPort |
  12. Elmets, CA, Bergstresser, PR, Tigelaar, RE, Wood, PJ, Streilein, JW: Analysis of the mechanism of unresponsiveness produced by hapten painted on skin exposed to ultraviolet radiation. J Exp Med 1983 158: 781–794,  | Article | PubMed | ISI | ChemPort |
  13. Streilein, JW, Bergstresser, PR: Genetic basis of ultraviolet-B effects on contact hypersensitivity. Immunogenetics 1988 27: 252–258,  | Article | PubMed | ISI | ChemPort |
  14. Yoshikawa, T, Streilein, JW: Concerning a possible link between the effect of UVB on contact hypersensitivity and the gene that dictates LPS responsiveness. J Invest Dermatol 1989 92: 547A,
  15. Fitzpatrick, TB: Ultraviolet induced pigmentary changes: Benefits and hazards. Curr Probl Dermatol 1986 15: 25–38,  | PubMed | ChemPort |
  16. Rae, V, Yoshikawa, T, Bruins-Slot, W, Streilein, JW, Taylor, JR: An ultraviolet B radiation protocol for complete depletion of human epidermal Langerhans cells. J Dermatol Surg Oncol 1989 15: 1199–1202,  | PubMed | ChemPort |
  17. Catalona, WJ, Taylor, PT, Chretien, PB: Quantitative dinitrochloro-benzene contact sensitization in a normal population. Clin Exp Immunol 1972 12: 325–333,  | PubMed | ChemPort |
  18. Flannigan, SA, Tucker, SB: Variation in cutaneous perfusion due to synthetic pyrethroid exposure. Br J Med 1985 11: 773–776,
  19. Mayerhausen, W, Remy, W: Testung der zellularen Immunreaktivitat bei Melanompatienten mit Diphenylcyclopropenon (DPCP) im Vergleigh mit Dinitrochlorobenzol (DNCB). Hautarzt 1987 38: 449–452,  | PubMed | ChemPort |
  20. Shultz, LD, Bailey, DW: Genetic control of contact sensitivity in mice effect of H-2 and non-H-2 loci. Immunogenetics 1975 1: 570–583,  | ISI |
  21. Olerup, O, Emtestam, L: Allergic contact dermatitis to nickel is associated with a Taq 1 HLA-DQA allelic restriction fragment. Immunogenetics 1988 28: 310–313,  | Article | PubMed | ChemPort |
  22. Waldorf, DS, Willkens, RF, Decker, JL: Impaired delayed hypersensitivity in an aging population. JAMA 1968 203: 831–834,  | Article | PubMed | ChemPort |
  23. Weimar, VM, Ceilley, RI, Goeken, JA: Cell-mediated immunity in patients with basal and squamous cell skin cancer. J Am Acad Dermatol 1980 2: 143–147,  | PubMed | ChemPort |
  24. Dellon, AL, Potvin, C, Chretien, PB, Rogentine, CN: The immunobiology of skin cancer. Plast Reconstr Surg 1975 55: 341–354,  | PubMed | ChemPort |
  25. Yunis, EJ, Fernandes, G, Greenberg, LJ: Tumor immunology, autoimmunity and aging. J Am Geriatrics Soc 1976 24: 258–263,  | ChemPort |
  26. Bergstresser, PR, Elmets, CA, Streilein, JW: Local effects of ultraviolet radiation on immune function in mice. In: Parish J (ed.): The Effect of Ultraviolet Light on the Immune System, Johnson and Johnson 1983, New Brunswick, NJ, pp 73–86,
  27. Kinlen, LF, Sheil, AGR, Peto, J, Doll, R: Collaborative United Kingdom-Australiasian study of cancer in patients treated with immunosuppressive drugs. Br J Med 1979 11: 1461–1466,
  28. Bouwes Bavinck, JN, Koote, AMM, Claas, FHJ, Vermeer, BJ: The association of major histocompatibility antigens with the occurrence of cutaneous epithelial malignancies in renal transplant recipients (abstr). J Invest Dermatol 1989 92: 407A,
  29. Kalish, RS, Morimoto, C: Quantitation and cloning of human urushiol specific peripheral blood T cells: isolation of urushiol triggered suppressor T cells. J Invest Dermatol 1989 92: 46–52,  | Article | PubMed | ChemPort |
  30. Cooper, KD, Baadsgaard, O, Salvo, B, Fox, D: Mechanisms of T suppressor cell generation by human UV-exposed epidermal cells (abstr). J Invest Dermatol 1990 94: 515A,
  31. Friedmann, PS, White, SI, Parker, S, Moss, C, Matthews, JNS: Antigenic stimulation during ultraviolet therapy in man does not result in immunological tolerance. Clin Exp Immunol 1989 76: 68–72,  | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT