Fig. 4.
MPO activity enhances mitoxantrone-induced TOP2-DNA covalent complex formation and H2AX phosphorylation. (A and B) NB4 cells were pretreated with 200 μM SA for 48 hours followed by a 1-hour incubation with 0.5 or 1 μM mitoxantrone, or a vehicle control. TOP2-DNA covalent complexes and γH2AX were quantified as in Figs. 1 and 3. Data are expressed relative to the mean values obtained with 1 μM mitoxantrone in the absence of SA. (C) Quantification of MPO activity in K562MPO line 2 compared with NB4 and parental K562 cells. (D) MPO expression in K562 cells results in enhanced mitoxantrone-induced TOP2-DNA protein complex formation. Data are expressed relative to the mean value obtained for parental K562 cells treated with 1 μM mitoxantrone. Numbers of replicates are indicated. *P < 0.05; **P < 0.01; ***P < 0.001.