Abstract
This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)- induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320- 500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aberer W., Leibl H. Effect of UVB radiation on the biosynthesis of HLA-DR antigens. Arch Dermatol Res. 1987;279(5):321–326. doi: 10.1007/BF00431225. [DOI] [PubMed] [Google Scholar]
- Ananthaswamy H. N., Fisher M. S. Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin. Cancer Res. 1981 May;41(5):1829–1833. [PubMed] [Google Scholar]
- Applegate L. A., Ley R. D. Ultraviolet radiation-induced lethality and repair of pyrimidine dimers in fish embryos. Mutat Res. 1988 Mar;198(1):85–92. doi: 10.1016/0027-5107(88)90043-7. [DOI] [PubMed] [Google Scholar]
- Applegate L. A., Stuart T. D., Ley R. D. Ultraviolet radiation-induced histopathological changes in the skin of the marsupial Monodelphis domestica. I. The effects of acute and chronic exposures and of photoreactivation treatment. Br J Dermatol. 1985 Aug;113(2):219–227. doi: 10.1111/j.1365-2133.1985.tb02068.x. [DOI] [PubMed] [Google Scholar]
- Cook J. S. Photoreactivation in animal cells. Photophysiology. 1970;5:191–233. [PubMed] [Google Scholar]
- Cook J. S., Regan J. D. Photoreactivation and photoreactivating enzyme activity in an order of mammals (Marsupialia). Nature. 1969 Sep 6;223(5210):1066–1067. doi: 10.1038/2231066a0. [DOI] [PubMed] [Google Scholar]
- Czernielewski J., Vaigot P., Asselineau D., Prunièras M. In vitro effect of UV radiation on immune function and membrane markers of human Langerhans cells. J Invest Dermatol. 1984 Jul;83(1):62–65. doi: 10.1111/1523-1747.ep12261699. [DOI] [PubMed] [Google Scholar]
- D'Ambrosio S. M., Whetstone J. W., Slazinski L., Lowney E. Photorepair of pyrimidine dimers in human skin in vivo. Photochem Photobiol. 1981 Oct;34(4):461–464. [PubMed] [Google Scholar]
- De Fabo E. C., Noonan F. P. Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology. J Exp Med. 1983 Jul 1;158(1):84–98. doi: 10.1084/jem.158.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eggset G., Volden G., Krokan H. U.v.-induced DNA damage and its repair in human skin in vivo studied by sensitive immunohistochemical methods. Carcinogenesis. 1983;4(6):745–750. doi: 10.1093/carcin/4.6.745. [DOI] [PubMed] [Google Scholar]
- Elmets C. A., Bergstresser P. R., Tigelaar R. E., Wood P. J., Streilein J. W. Analysis of the mechanism of unresponsiveness produced by haptens painted on skin exposed to low dose ultraviolet radiation. J Exp Med. 1983 Sep 1;158(3):781–794. doi: 10.1084/jem.158.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FAN J., SCHOENFELD R. J., HUNTER R. A study of the epidermal clear cells with special reference to their relationship to the cells of Langerhans. J Invest Dermatol. 1959 Mar;32(3):445–450. doi: 10.1038/jid.1959.74. [DOI] [PubMed] [Google Scholar]
- Fadem B. H., Trupin G. L., Maliniak E., VandeBerg J. L., Hayssen V. Care and breeding of the gray, short-tailed opossum (Monodelphis domestica) Lab Anim Sci. 1982 Aug;32(4):405–409. [PubMed] [Google Scholar]
- Fisher M. S., Menter J. M., Willis I. Ultraviolet radiation-induced suppression of contact hypersensitivity in relation to padimate O and oxybenzone. J Invest Dermatol. 1989 Mar;92(3):337–341. doi: 10.1111/1523-1747.ep12277156. [DOI] [PubMed] [Google Scholar]
- Grube D. D., Ley R. D., Fry R. J. Photosensitizing effects of 8-methoxypsoralen on the skin of hairless mice--II. Strain and spectral differences for tumorigenesis. Photochem Photobiol. 1977 Mar;25(3):269–276. doi: 10.1111/j.1751-1097.1977.tb06910.x. [DOI] [PubMed] [Google Scholar]
- HANISZKO J., SUSKIND R. R. The effect of ultraviolet radiation on experimental cutaneous sensitization in guineapigs. J Invest Dermatol. 1963 Apr;40:183–191. doi: 10.1038/jid.1963.35. [DOI] [PubMed] [Google Scholar]
- Howie S., Norval M., Maingay J. Exposure to low-dose ultraviolet radiation suppresses delayed-type hypersensitivity to herpes simplex virus in mice. J Invest Dermatol. 1986 Feb;86(2):125–128. doi: 10.1111/1523-1747.ep12284128. [DOI] [PubMed] [Google Scholar]
- Iacobelli D., Hashimoto K., Takahashi S. Effect of ultraviolet radiation on guinea pig epidermal Langerhans cell cytomembrane: light and electron microscopic studies. Photodermatol. 1985 Jun;2(3):132–143. [PubMed] [Google Scholar]
- Kripke M. L. Immunological unresponsiveness induced by ultraviolet radiation. Immunol Rev. 1984 Aug;80:87–102. doi: 10.1111/j.1600-065x.1984.tb00496.x. [DOI] [PubMed] [Google Scholar]
- LeVee G. J., Applegate L. A., Ley R. D. Photoreversal of the ultraviolet radiation-induced disappearance of ATPase-positive Langerhans cells in the epidermis of Monodelphis domestica. J Leukoc Biol. 1988 Dec;44(6):508–513. doi: 10.1002/jlb.44.6.508. [DOI] [PubMed] [Google Scholar]
- Ley R. D., Applegate L. A., Freeman S. E. Photorepair of ultraviolet radiation-induced pyrimidine dimers in corneal DNA. Mutat Res. 1988 Jul;194(1):49–55. doi: 10.1016/0167-8817(88)90055-7. [DOI] [PubMed] [Google Scholar]
- Ley R. D., Applegate L. A. Loss of photoreversibility of sunburn cell induction in Monodelphis domestica. Photochem Photobiol. 1987 Aug;46(2):315–317. doi: 10.1111/j.1751-1097.1987.tb04773.x. [DOI] [PubMed] [Google Scholar]
- Ley R. D., Applegate L. A. Ultraviolet radiation-induced histopathologic changes in the skin of the marsupial Monodelphis domestica. II. Quantitative studies of the photoreactivation of induced hyperplasia and sunburn cell formation. J Invest Dermatol. 1985 Oct;85(4):365–367. doi: 10.1111/1523-1747.ep12276992. [DOI] [PubMed] [Google Scholar]
- Ley R. D. Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2409–2411. doi: 10.1073/pnas.82.8.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ley R. D., Sedita A., Grube D. D., Fry R. J. Induction and persistence of pyrimidine dimers in the epidermal DNA of two strains of hairless mice. Cancer Res. 1977 Sep;37(9):3243–3248. [PubMed] [Google Scholar]
- Ley R. D., Sedita B. A., Grube D. D. Absence of photoreactivation of pyrimidine dimers in the epidermis of hairless mice following exposures to ultraviolet light. Photochem Photobiol. 1978 Apr;27(4):483–485. doi: 10.1111/j.1751-1097.1978.tb07633.x. [DOI] [PubMed] [Google Scholar]
- Mitchell D. L., Clarkson J. M., Chao C. C., Rosenstein B. S. Repair of cyclobutane dimers and (6-4) photoproducts in ICR 2A frog cells. Photochem Photobiol. 1986 May;43(5):595–597. doi: 10.1111/j.1751-1097.1986.tb09539.x. [DOI] [PubMed] [Google Scholar]
- Morison W. L., Bucana C., Kripke M. L. Systemic suppression of contact hypersensitivity by UVB radiation is unrelated to the UVB-induced alterations in the morphology and number of Langerhans cells. Immunology. 1984 Jun;52(2):299–306. [PMC free article] [PubMed] [Google Scholar]
- Morison W. L., Kelley S. P. Urocanic acid may not be the photoreceptor for UV-induced suppression of contact hypersensitivity. Photodermatol. 1986 Apr;3(2):98–101. [PubMed] [Google Scholar]
- Morison W. L., Kripke M. L. Systemic suppression of contact hypersensitivity by ultraviolet b radiation or methoxsalen/ultraviolet a radiation in the guinea pig. Cell Immunol. 1984 Apr 15;85(1):270–277. doi: 10.1016/0008-8749(84)90298-3. [DOI] [PubMed] [Google Scholar]
- Morrison H. Photochemistry and photobiology of urocanic acid. Photodermatol. 1985 Jun;2(3):158–165. [PubMed] [Google Scholar]
- Noonan F. P., Bucana C., Sauder D. N., De Fabo E. C. Mechanism of systemic immune suppression by UV irradiation in vivo. II. The UV effects on number and morphology of epidermal Langerhans cells and the UV-induced suppression of contact hypersensitivity have different wavelength dependencies. J Immunol. 1984 May;132(5):2408–2416. [PubMed] [Google Scholar]
- Noonan F. P., De Fabo E. C., Kripke M. L. Suppression of contact hypersensitivity by UV radiation and its relationship to UV-induced suppression of tumor immunity. Photochem Photobiol. 1981 Dec;34(6):683–689. [PubMed] [Google Scholar]
- Noonan F. P., De Fabo E. C., Morrison H. Cis-urocanic acid, a product formed by ultraviolet B irradiation of the skin, initiates an antigen presentation defect in splenic dendritic cells in vivo. J Invest Dermatol. 1988 Feb;90(2):92–99. doi: 10.1111/1523-1747.ep12462045. [DOI] [PubMed] [Google Scholar]
- Nordlund J. J., Ackles A. E., Lerner A. B. The effects of ultraviolet light and certain drugs on La-bearing Langerhans cells in murine epidermis. Cell Immunol. 1981 May 1;60(1):50–63. doi: 10.1016/0008-8749(81)90247-1. [DOI] [PubMed] [Google Scholar]
- Okamoto H., Kripke M. L. Effector and suppressor circuits of the immune response are activated in vivo by different mechanisms. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3841–3845. doi: 10.1073/pnas.84.11.3841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parrish J. A., Jaenicke K. F., Anderson R. R. Erythema and melanogenesis action spectra of normal human skin. Photochem Photobiol. 1982 Aug;36(2):187–191. doi: 10.1111/j.1751-1097.1982.tb04362.x. [DOI] [PubMed] [Google Scholar]
- Robertson B., Gahring L., Newton R., Daynes R. In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function. J Invest Dermatol. 1987 Apr;88(4):380–387. doi: 10.1111/1523-1747.ep12469071. [DOI] [PubMed] [Google Scholar]
- Ross J. A., Howie S. E., Norval M., Maingay J., Simpson T. J. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice. J Invest Dermatol. 1986 Nov;87(5):630–633. doi: 10.1111/1523-1747.ep12456257. [DOI] [PubMed] [Google Scholar]
- Schwarz T., Urbanska A., Gschnait F., Luger T. A. Inhibition of the induction of contact hypersensitivity by a UV-mediated epidermal cytokine. J Invest Dermatol. 1986 Aug;87(2):289–291. doi: 10.1111/1523-1747.ep12696708. [DOI] [PubMed] [Google Scholar]
- Sutherland B. M., Harber L. C., Kochevar I. E. Pyrimidine dimer formation and repair in human skin. Cancer Res. 1980 Sep;40(9):3181–3185. [PubMed] [Google Scholar]
- Toews G. B., Bergstresser P. R., Streilein J. W. Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol. 1980 Jan;124(1):445–453. [PubMed] [Google Scholar]
- Zelle B., Reynolds R. J., Kottenhagen M. J., Schuite A., Lohman P. H. The influence of the wavelength of ultraviolet radiation on survival, mutation induction and DNA repair in irradiated Chinese hamster cells. Mutat Res. 1980 Aug;72(3):491–509. doi: 10.1016/0027-5107(80)90121-9. [DOI] [PubMed] [Google Scholar]