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 drug mitoxantrone (MXN), among them an interaction mediated by the cleavable DNA topoisomerase II complex. Cotreatment of human peripheral blood lymphocyte cultures from six donors with MXN (12 x 10(-6) micrograms/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, treatment with MXN and novobiocin (10 micrograms/ml), a non-specific DNA topoisomerase II inhibitor, led to a decrease in the chromosome aberrations induced by MXN in the G2 phase of the cell cycle.
Medeiros M das
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Dep. de Genética, Universidade Federal do Rio Grande do Norte-UFRN, Natal, RN, Brazil.
Takahashi
C S
CS
D000328:Adult; D002110:Caffeine / Q000494:pharmacology*; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology*; D009675:Novobiocin / Q000494:pharmacology*
D003561:Cytarabine; D009675:Novobiocin; D002110:Caffeine; D008942:Mitoxantrone