Abstract: Novel thymidylate synthase (TS mutants) are disclosed differing from human wild type thymidylate synthase in single, double, or multiple mutations, which show intact enzyme activity and enhanced resistance to TS-inhibiting drugs like 5-fluorouracil or 5-fluoro-2-deoxyuridinemonophosphate. All these mutants can be used for the protection of normal human cell populations against the toxic manifestation of analogs that inhibited TS. Drugs for the local treatment or prevention of a mucositis in the oral cavity and the gastrointestinal tract caused by chemotherapy with TS-inhibitors are also provided.

Abstract: The invention relates to a medicament for locally treating or preventing a mucositis, which is induced by chemotherapy with thymidylate synthase inhibitors, in the oral cavity and in the gastrointestinal tract, whereby a thymidylate synthase mutant, which is coupled to a transductor for the transduction into a cell, which has an intact enzyme activity, and which is resistant to thymidylate synthase inhibitors, is administered.