The study of factors controlling the generation of cutaneous injuries, both intradermal and topical, from the antitumor agent, mitomycin C, is proposed. This drug is a source of health hazard for occupation related injuries in health care workers, and treatment related injuries in cancer patients. Current and projected usage of mitomycin C indicate a substantial potential risk of cutaneous injury, with present treatment methods unsatisfactory. The studies will be undertaken in a murine model. Factors of injury generation will be investigated first, and include: drug dose; concentration; injury generation time; healing time; rate of drug activation in dermal tissues; and clinicopathologic correlations. On completion of the work on parameters of injury generation, additional studies of factors and treatment measures that will reduce, prevent, or eliminate cutaneous injury from the use of mitomycin antitumor agents are proposed. Factors to be investigated for possible benefit against mitomycin C cutaneous injury include: cutidotal measures, such as DMSO; and measures designed to reduce drug activation, directed against both reductive activation and acidic activation. These studies will also be undertaken in a murine model.
