The crosslinking of proteins to DNA has been proposed as a mechanism for aging and carcinogenesis, but the biological importance of these crosslinks has remained unclear. We have employed a transfection system to demonstrate that: 1) sensitivity of DNA to biological inactivation by ultraviolet radiation is altered by the presence of proteins or amino acids, 2) this effect apparently does not require covalent crosslink formation, 3) UV sensitivity of DNA in buffer and in solutions of amino acids is a function of the cation concentration of the buffer. The mechanisms by which proteins alter UV sensitivity of DNA remain unclear. This research will: 1) identify the protein-DNA interactions which contribute to UV sensitization of DNA by proteins, 2) determine whether proteins can enhance the production of non-crosslink lesions, attempt to identify cellular enzyme systems capable of detecting and repairing DNA-protein crosslinks, 4) evaluate the transfection system for its ability to elucidate interactions between specific initiators and promoters of carcinogenesis.