The broad goal of this research is to gain a better understanding of the molecular basis for the dermatological phototoxicity of the tetracycline family of drugs. These drugs, among the most widely prescribed family of antibiotics, represent a virtually classic example of such phototoxicity. The objectives of the program include the complete delineation of (a) tetracycline's unimolecular photochemistry and (b) the covalent binding of tetracycline photoproducts to nucleic acids. Specifically, the program will (1) complete the identification of "lumitetracycline", a new photoproduct isolated in these laboratories which gives evidence for possible greater phototoxicity than tetracycline itself, (2) determine the mechanistic details of tetracycline's photochemistry, (3) identify the photoproducts formed from tetracycline which covalently bind to DNA in the dark, (4) determine the bases which are the targets for such binding and the chemical reactions involved and (5) extend our studies to the photochemistry and photobiology of lumitetracycline in order to establish the origin of this molecule's recently determined mitochondrial phototoxicity.