Abstract
Immunogenic murine tumours that are normally rejected upon transplantation into syngeneic hosts grow progressively if the hosts are UV-irradiated prior to tumour implantation. Using three sources of UV we investigated the most effective waveband and dose for increased outgrowth of injected fibrosarcoma (FSA) cells in mice, compared with unirradiated controls. The animals were exposed on their shaved dorsal skin twice a week for 3 weeks to either broad-band (TL12) or narrow-band (TL01) UVB, or UVA-I radiation; FSA cells were then injected subcutaneously into the UV-irradiated skin. Exposure to TL12 at doses higher than 1000 J m−2, but not TL01 or UVA-I, caused increased outgrowth of the injected tumour cells. The effect of the UV irradiation seemed to be local as injection of the FSA cells into the unirradiated ventral skin of mice irradiated with TL12 on the dorsal surface did not result in increased outgrowth of the tumours. Cis-urocanic acid, a recognised initiator of UV-induced immunosuppression, applied topically or intradermally for 3 weeks prior to FSA cell injection, had no effect on the rate of tumour outgrowth. Similarly, injection of a monoclonal antibody with specificity for cis-urocanic acid, prior to each irradiation with TL12, did not reverse the increased growth of FSA cells injected into the UV-irradiated skin. Thus wavelengths within the broad-band UVB range are the most effective for inducing increased outgrowth of FSA cells; cis-urocanic acid is not an important mediator in this UV-enhanced growth of tumours.
Similar content being viewed by others
References
M. L. Kripke, Antigenicity of murine skin tumours induced by ultraviolet light, J. Natl. Cancer Inst., 1974, 53, 1333–1336.
M. L. Kripke, M. S. Fisher, Immunologic parameters of ultraviolet carcinogenesis, J. Natl. Cancer Inst., 1976, 57, 211–215.
C. W. Spellman, R. A. Daynes, Modification of immunological potential by ultraviolet radiation: II. Generation of suppressor cells in short-term UV-irradiated mice, Transplantation, 1977, 24, 120–126.
E. C. De Fabo, M. L. Kripke, Wavelength dependence and dose-rate independence of UV radiation-induced immunologic unresponsiveness of mice to a UV-induced fibrosarcoma, Photochem. Photobiol., 1980, 32, 183–188.
F. R. de Gruijl, H. J. C. M. Sterenborg, P. D. Forbes, R. E. Davies, C. Cole, G. Kelfkens, H. vanweelden, H. Slaper, J. C. van der Leun, Wavelength dependence of skin-cancer induction by ultraviolet-irradiation of albino hairless mice, Cancer Res., 1993, 53, 53–60.
S. E. Ullrich, The role of epidermal cytokines in the generation of cutaneous immune-reactions and ultraviolet radiation-induced immune suppression, Photochem. Photobiol., 1995, 62, 389–401.
A. A. El-Ghorr, F. Pierik, M. Norval, Comparative potency of different UV sources in reducing the density and antigen-presenting capacity of Langerhans cells in mice, Photochem. Photobiol., 1994, 60, 256–261.
W. Goettsch, H. M. H. Hurks, J. Garssen, A. M. Mommaas, W. Slob, J. Hoekman, F. Pierik, P. J. M. Roholl, H. Van Loveren, Comparative immunotoxicology of ultraviolet B exposure–I. Effects of in vitro and in situ ultraviolet B exposure on the functional activity and morphology of Langerhans cells in the skin of different species, Br. J. Dermatol., 1998, 139, 230–238.
A. M. Moodycliffe, D. Nghiem, G. Clydesdale, S. E. Ullrich, Immune suppression and skin cancer development: regulation by NKT cells, Nat. Immunol., 2000, 1, 521–525.
A. Schwarz, S. Beissert, K. Grosse-Heitmeyer, M. Gunzer, J. A. Bluestone, S. Grabbe, T. Schwarz, Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced tolerance, J. Immunol., 2000, 165, 1824–1831.
M. L. Kripke, P. A. Cox, L. G. Alas, D. B. Yarosh, Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice, Proc. Natl. Acad. Sci. USA, 1992, 89, 7516–7520.
E. C. De Fabo, F. P. Noonan, Mechanism of immune suppression by ultraviolet irradiation in vivo 1. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology, J. Exp. Med., 1983, 157, 84–98.
T. Mohammad, H. Morrison, H. HogenEsch, Urocanic acid photochemistry and photobiology, Photochem. Photobiol., 1999, 69, 115–135.
V. E. Reeve, M. Bosnic, C. Boehm-Wilcox, N. Nishimura, R. D. Ley, Ultraviolet A radiation (320–400 nm) protects hairless mice from immunosuppression induced by ultraviolet B radiation (280–320 nm) or cis-urocanic acid, Int. Arch. Allergy Immunol., 1998, 115, 316–322.
A. A. El-Ghorr, M. Norval, The UV waveband dependencies in mice differ for the suppression of contact hypersensitivity, delayed-type hypersensitivity and cis-urocanic acid formation, J. Invest. Dermatol., 1999, 112, 757–762.
I. Iwai, M. Hatao, M. Naganuma, Y. Kumano, M. Ichihashi, UVA-induced immune suppression through an oxidative pathway, J. Invest. Dermatol., 1999, 112, 19–24.
H. D. Suit, A. Kastelan, Immunologic status of host and response of a methylcholanthrene-induced sarcoma to local x-irradiation, Cancer, 1970, 26, 232–238.
W. H. McBride, J. D. Thacker, S. Comora, J. S. Economou, D. Kelley, D. Hogge, S. M. Dubinett, G. J. Dougherty, Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumour immunity, Cancer Res., 1992, 52, 3931–3937.
M. Norval, T. J. Simpson, E. Bardshiri, S. E. M. Howie, Urocanic acid analogs and the suppression of the delayed-type hypersensitivity response to herpes-simplex virus, Photochem. Photobiol., 1989, 49, 633–639.
A. M. Moodycliffe, M. Norval, I. Kimber, T. J. Simpson, Characterization of a monoclonal antibody to cis-urocanic acid–detection of cis-urocanic acid in the serum of irradiated mice by immunoassay, Immunology, 1993, 79, 667–672.
V. E. Reeve, G. E. Greenoak, P. J. Canfield, C. Boehm-wilcox, C. H. Gallagher, Topical urocanic acid enhances UV-induced tumor yield and malignancy in the hairless mouse, Photochem. Photobiol., 1989, 49, 459–464.
A. M. Moodycliffe, C. D. Bucana, M. L. Kripke, M. Norval, S. E. Ullrich, Differential effects of a monoclonal antibody to cis-urocanic acid on the suppression of delayed and contact hypersensitivity following ultraviolet irradiation, J. Immunol., 1996, 157, 2891–2899.
A. L. P. Caforio, A. B. Fortina, A. Gambino, S. Piaserico, G. Feltrin, F. Tona, E. Pompei, L. Testolin, F. Gai, A. Angelini, D. Casarotto, A. Peserico, High rejection score in the first year and risk of skin cancer in heart transplantation, Transplant. Proc., 2001, 33, 1608–1609.
J. Boyle, R. M. Mackie, J. D. Briggs, B. J. R. Junor, T. C. Aitchison, Cancer, warts and sunshine in renal-transplant patients–a case control study, Lancet, 1984, 1, 702–705.
F. R. de Gruijl, UV radiation and tumour immunity, Methods, 2002, 28, 122–129.
M. S. Fisher, M. L. Kripke, Further studies on the tumour-specific suppressor cells induced by ultraviolet radiation, J. Immunol., 1978, 121, 1139–1144.
C. A. Romerdahl, C. Donawho, I. J. Fidler, M. L. Kripke, Effect of ultraviolet-B radiation on the in vivo growth of murine melanoma cells, Cancer Res., 1988, 48, 4007–4010.
M. S. Fisher, M. L. Kripke, Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice, Science, 1982, 216, 1133–1134.
F. Aubin, C. K. Donawho, M. L. Kripke, Effect of psoralen plus ultraviolet A radiation on in vivo growth of melanoma cells, Cancer Res., 1991, 51, 5893–5897.
R. D. Ley, Dose response for ultraviolet radiation A-induced focal melanocytic hyperplasia and nonmelanoma skin tumors in Monodelphis domestica, Photochem. Photobiol., 2001, 73, 20–23.
S. Beissert, T. Mohammad, H. Torri, A. Lonati, Z. M. Yan, H. Morrison, R. D. Granstein, Regulation of tumor antigen presentation by urocanic acid, J. Immunol., 1997, 159, 92–96.
S. Beissert, D. Ruhlemann, T. Mohammad, S. Grabbe, A. El-Ghorr, M. Norval, H. Morrison, R. D. Granstein, T. Schwarz, IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: Implications for photocarcinogenesis, J. Immunol., 2001, 167, 6232–6238.
A. Kammeyer, T. A. Eggelte, H. Overmars, A. Bootsma, J. D. Bos, M. B. M. Teunissen, Oxidative breakdown and conversion of urocanic acid isomers by hydroxyl radical generating systems, Biochim. Biophys. Acta-Gen. Subjects, 2001, 1526, 277–285.
A. A. El-Ghorr, M. Norval, M. B. Lappin, J. C. Crosby, The effect of chronic low-dose UVB radiation on Langerhans cells, sunburn cells, urocanic acid isomers, contact hypersensitivity and serum inmmunoglobulins in mice, Photochem. Photobiol., 1995, 62, 326–332.
A. A. El-Ghorr, M. Norval, A monoclonal antibody to cis-urocanic acid prevents the ultraviolet-induced changes in Langerhans cells and delayed-hypersensitivity responses in mice, although not preventing dendritic cell accumulation in lymph-nodes draining the site of irradiation and contact hypersensitivity responses, J. Invest. Dermatol., 1995, 105, 264–268.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Macve, J.C., Norval, M. The effects of UV waveband and cis-urocanic acid on tumour outgrowth in mice. Photochem Photobiol Sci 1, 1006–1011 (2002). https://doi.org/10.1039/b208247k
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/b208247k