Cytostatic synergism between bromodeoxyuridine, bleomycin, cisplatin and chlorambucil demonstrated by a sensitive cell kinetic assay

Bromodeoxyuridine/Hoechst flow cytometry was used to analyse the interference of common cytostatic agents with cell activation and cell cycle progression of human B-cell lines. Bleomycin impaired both cell activation and G2 transit, the latter effect being oxygen dependent. The DNA alkylating agents cyclophosphamide, chlorambucil and mitomycin C caused G2 arrest, whereas cisplatin arrested cells in both the S and G2 phase of the cell cycle. Vinblastin interfered with mitosis, but in addition arrested cells in all phases of the cell cycle. The growth inhibitory action of bleomycin, cisplatin and chlorambucil was dependent upon the bromodeoxyuridine (BrdU) concentration in the culture medium. No interaction was found between BrdU and cyclophosphamide, mitomycin C and vinblastin. The cell cycle kinetic mechanism of the interaction between BrdU and bleomycin, cisplatin and chlorambucil was a potentiation of the G2 arrest. In conclusion, BrdU may be useful in clinical chemotherapy as a chemosensitizer for selected cytostatic agents.