156 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS contribute to cellular damage (22), and it is possible that this photoreactive pathway contributes to the immunosuppressive characteristics exhibited by urocanic acid. The data summarized herein provides experimental evidence to the Cosmetic Review Expert Panel and to those who use urocanic acid as an ingredient in cosmetic agents that long-lived reactive intermediates do exist following absorption of solar UV by urocanic acid. The effects of these intermediates should be explored further to determine their significance in vivo, where, because both isomers of urocanic acid generate triplet state and singlet oxygen intermediates in the UV-B, both should be of concern when con- sidering urocanic acid as an additive to topical formulations. ACKNOWLEDGMENTS This work is supported by the Institute of General Medicine of NIH and by a graduate fellowship from ARCS. We are grateful to Professor Doug Magde for the use of his Excimer laser, to Professor Roger Tsien for the use of his fluorometer, and to Dr. Bulang Li for technical assistance. REFERENCES (1) A. Zenisk and J. A. Kral, The occurrence of urocanic acid in human sweat, Blochim. Biophys. Acta, 12, 479-480 (1953). (2) A. Zenisk, J. A. Kral, and I. M. Hals, "Sun-screening" effect of urocanic acid, Blochim. Biophys. Acta, 18, 589-591 (1955). (3) Cosmetic Ingredient Review Expert Panel, Cosmetic ingredient review final report on the safety assessment of urocanic acid, J. Am. Coil. ToxicoL, 14, 386-421 (1995). (4) J. H. Anglin, Jr., A. T. Bever, M. A. Everett, and J. M. Lamb, Ultraviolet-light-induced alterations in urocanic acid in vivo, Blochim. Biophys. Acta, 53, 408-409 (1961). (5) E. C. De Fabo and F. P. Noonan, Mechanism of immune suppression by ultraviolet irradiation in vivo. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology,J. Exp. Med., 157, 84-98 (1983). (6) M. Norval, N. K. Gibbs, and J. Gilmour, The role of urocanic acid in UV-induced immunosuppres- sion: Recent advances (1992-1994), Photochem. PhotobioL, 62, 209-217 (1995). (7) A. El-ghorr, F. Pierik, and M. Norval, Comparative potency of different UV sources in reducing the density and antigen presenting capacity of murine Langerhans cells, Photochem. PhotobioL, 60, 256-261 (1994). (8) I. Kurimoto and J. W. Streilein, Cis-urocanic acid suppression of contact hypersensitivity is mediated via tumor necrosis factor-alpha, J. lmmunoL, 148, 3072-3078 (1992). (9) M. Norval, T.J. Simpson, E. Bardshiri, and S. E. M. Howie, Urocanic acid analogues and the sup- pression of the delayed hypersensitive response to herpes simplex virus, Photochem. PhotobioL, 49, 633-639 (1989). (10) J. W. Gilmour and M. Norval, The effect of UVB irradiation, cis-urocanic acid, and turnout necrosis factor-alpha on delayed hypersensitivity to herpes simplex virus, PhotodermatoL PhotoimmunoL Photoreed., 9, 250-259 (1993). (11) J. w. Gilmour, J.P. Vestey, S. George, and M. Norval, The effect of phototherapy and urocanic acid on natural killer cell function, J. Invest. DermatoL, 101, 169-174 (1993). (12) R. H. Guymer and T. E. Mandel, Urocanic acid as an immunosuppressant in allotransplantation in mice, Transplantation, 55, 36-43 (1993). (13) K. M. Hanson, B. Li, and J. D. Simon, A spectroscopic study of the epidermal ultraviolet chromophore trans-urocanic acid, JACS, 119, 2715-2721 (1997). (14) F. P. Noonan, private communication. (15) J. H. Anglin and M. A. Everett, Photodimerization of urocanic acid in vitro and in vivo, Biochim. Biophys. Acta, 88, 492-501 (1964).
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