melphalan and aziridine

The cytotoxicity of oxaziridines photogenerated after irradiation of chlordiazepoxide (CDZ) and its metabolites was investigated in vitro by a MTT assay on P388 leukemia and B16 melanoma cell lines and compared with that of the anticancer drug, melphalan. For the longer time-exposure experiment, oxaziridines had the same cytotoxicity as melphalan and this toxicity was higher when oxaziridines were photogenerated in the presence of cells. In conclusion, oxaziridines generated after CDZ, demoxepam, and desmethylchlordiazepoxide ultraviolet irradiation exhibited cytotoxicity activity against cancer cell lines. A possibility of CDZ use within the context of photodynamic therapy as a treatment for small, superficial tumors should not be excluded, because oxaziridines can be generated locally by skin-tumor local irradiation after CDZ topical administration.

Topics: Animals; Aziridines; Benzodiazepines; Cell Line; Cell Survival; Chlordiazepoxide; Drug Screening Assays, Antitumor; Female; Humans; Leukemia P388; Male; Melanoma, Experimental; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Radiation; Ultraviolet Rays

A diaziridinylspermine analogue, 1,12-diaziridinyl-4,9-diazadodecane (NSC-667005), was synthesized as a bisalkylating agent with a polyamine backbone. DNA cross-linking was detected in the reaction of linearized pBR322 DNA with 1,12-diaziridinyl-4,9-diazadodecane at concentrations comparable with that required for cross-linking by two nitrogen mustard drugs, mechlorethamine and melphalan. A significant increase in life span of female CD2F1 mice bearing L1210 murine leukemia was observed after intravenous administration of 1,12-diaziridinyl-4,9-diazadodecane in doses of less than 2.7 mg/kg, given on days 1, 5, and 9 of treatment.

Topics: Animals; Antineoplastic Agents; Aziridines; Cross-Linking Reagents; DNA; Electrophoresis, Agar Gel; Female; Leukemia L1210; Mechlorethamine; Melphalan; Mice; Mice, Inbred Strains; Spermine; Thiotepa

Mutagenic effect of vincristine, vinblastine, thiophosphamide, sarcolysine and the supermutagen ethyleneimine was studied in Crepis capillaris germinating seeds at the G phase. Metabolic conditions, prolongation of cell cycle, specific activity of preparation as well as inhibition of DNA synthesis were found to modify the mutagenic process induced by antitumour agents.

Topics: Antineoplastic Agents; Aziridines; Chromosome Aberrations; Interphase; Melphalan; Mutagens; Plants; Thiotepa; Vinblastine; Vincristine