[DNA and chromatin defects induced by thiophosphamide].

Treatment of mouse embryo fibroblasts with thio-TEPA (100 micrograms/ml) induced the formation of DNA interstrand cross-links after 10 hours and of DNA one-strand breaks after 20 hours. A short-term incubation of the cells with high concentrations of thio-TEPA (1 mg/ml, 30 min) resulted in a gradual increase of DNA cross-linking, which reached its maximal value after 4 hours of post-incubation. The cross-linking of DNA as well as the formation of DNA one-strand breaks was accompanied by a weakening of DNA-protein interactions in the chromatin. The prolonged existence of DNA and chromatin lesions is supposed to be an important step in the molecular mechanism of action of thio-TEPA.