EFFECTS OF TREATMENT WITH MITOXANTRONE IN COMBINATION WITH NOVOBIOCIN, CAFFEINE AND ARA-C ON HUMAN-LYMPHOCYTES IN CULTURE

Many cytotoxic mechanisms have been proposed for the antineoplastic dr ug mitoxantrone (MXN), among them an interaction mediated by the cleav able DNA topoisomerase II complex. Cotreatment of human peripheral blo od lymphocyte cultures from six donors with MXN (12 X 10(-6) mu g/ml) and the inhibitors of DNA repair or synthesis, caffeine (10(-3) M) and ara-C (5 x 10(-6) M) administered as 30-min pulses did not potentiate the clastogenic effect of MXN on this biological system. However, tre atment with MXN and novobiocin (10 mu g/ml), a non-specific DNA topois omerase II inhibitor, led to a decrease in the chromosome aberrations induced by MXN in the G(2) phase of the cell cycle.