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Pyrimidine Dimer Removal Enhanced by DNA Repair Liposomes Reduces the Incidence of UV Skin Cancer in Mice¹

Applied Genetics Inc., Freeport, New York 11520 [D. Y., L. G. A., V. Y., A. O., J. T. K.]; Laboratory of Radiobiology, University of California, San Francisco, California 94143 [D. M.]; Eye Research Institute, Boston, Massachusetts 02114 [R. R.]; and Department of Hematology/Oncology, Long Island Jewish Medical Center, New Hyde Park, New York 11042 [M. C.]

UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.

¹ Supported in part by National Cancer Institute Small Business Innovative Research Grant 2-R44-CA52401-01 to Applied Genetics Inc.

² To whom requests for reprints should be addressed, at Applied Genetics Inc., 205 Buffalo Avenue, Freeport, NY 11520.

³ Present address: Wise Hall, Ohio State University, Columbus, OH 43210.

⁴ Present address: University of Texas, M. D. Anderson Science Park, Research Division, P. O. Box 389, Smithville, TX 78957.

Received 12/18/91. Accepted 5/12/92.

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