Molecular Targets for UVR-Induced Skin Effects Epidermal DNA, predominantly in keratinocytes and in Langerhans cells (LCs), which are dendritic antigen-presenting cells, absorbs UV-B and undergoes structural changes including the formation of cyclobutane dimers and 6,4photoproducts. These structural changes are potentially mutagenic and can be repaired by mechanisms that result in their recognition and excision and the reestablishment of normal base sequences. The efficient repair of these structural aberrations is crucial, since individuals with defective DNA repair are at high risk for the development of cutaneous cancer. . | Chapter 057. Photosensitivity and Other Reactions to Light Part 2 Molecular Targets for UVR-Induced Skin Effects Epidermal DNA predominantly in keratinocytes and in Langerhans cells LCs which are dendritic antigen-presenting cells absorbs UV-B and undergoes structural changes including the formation of cyclobutane dimers and 6 4-photoproducts. These structural changes are potentially mutagenic and can be repaired by mechanisms that result in their recognition and excision and the reestablishment of normal base sequences. The efficient repair of these structural aberrations is crucial since individuals with defective DNA repair are at high risk for the development of cutaneous cancer. For example patients with xeroderma pigmentosum XP an autosomal recessive disorder are characterized by variably deficient repair of UV-induced photoproducts and their skin phenotype often manifests the dry leathery appearance of prematurely photoaged skin as well as basal cell and squamous cell carcinomas and melanoma in the first two decades of life. Studies in mice using knockout gene technology have verified the importance of functional genes regulating these repair pathways in preventing the development of UV-induced cancer. Furthermore incorporation of a bacterial DNA repair enzyme T4N5 endonuclease into liposomes in a product applied to skin of patients with XP selectively removes cyclobutane pyrimidine dimers and reduces the degree of solar damage and skin cancer. DNA damage in LCs may contribute to the known immunosuppressive effects of UV-B see Immunologic Effects below . Cutaneous Optics and Chromophores Chromophores are endogenous or exogenous chemical components that can absorb physical energy. Endogenous chromophores are of two types 1 chemicals that are normal components of skin including nucleic acids proteins lipids and 7-dehydrocholesterol the precursor of vitamin D and 2 chemicals such as porphyrins synthesized elsewhere in the body that circulate in the bloodstream
