Md. Medeiros et Cs. Takahashi, EFFECTS OF TREATMENT WITH MITOXANTRONE IN COMBINATION WITH NOVOBIOCIN, CAFFEINE AND ARA-C ON HUMAN-LYMPHOCYTES IN CULTURE, MUTATION RESEARCH, 307(1), 1994, pp. 285-292
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.