The induction and repair of cyclobutane thymidine dimers in human skin

The most important detrimental effect of ultraviolet radiation (UV) on the living cell, so far known, is the induction of damage in the DNA. The major photoproducts induced in DNA by UV-C (200-280 nm) and UV-B (280-315 nm) are the cyclobutane-type pyrimidine dimers, which have been implicated in UV-induced mutagenesis and carcinogenesis. Dimer lesions in DNA of cells may be repaired in the dark by a multi-enzyme process (excision repair), or via a light dependent enzymatic reaction known as photoreactivation (phr) which is specific for pyrimidine dimers. Although phr has been found to occur in a wide range of organisms, studies on the presence of phr in mammalian cells have yielded conflicting results. To investigate repair of pyrimidine dimers in human skin cells irradiated in vivo, a specific and sensitive detection method was developed based on a monoclonal antibody directed against thymidine dimers. Application together with a fluorescent immunostaining permits the direct detection of thymidine dimers in human skin cells. The method is used in studies aimed at a better understanding of the role of these lesions in the process of carcinogenesis. A report is given on the isolation and characterization of the antibodies, and their application in a study on the induction of pyrimidine dimers in human skin and on photorepair in cultured cells. 10 refs.; 2 figs