Mechanisms of Anthracycline-Enhanced Reactive Oxygen Metabolism in Tumor Cells

Figure 1

Effect of doxorubicin on oxygen consumption by Ehrlich tumor organelles. Oxygen consumption in tumor microsomes was examined as described in Supplementary Table 1. (a, i) is without drug; (ii) shows the results with doxorubicin. The addition of NADPH (1 mM), catalase (4500 units), or doxorubicin (135 μM) to the 3 ml vessel was performed through the access slot of the oxygen electrode and has been indicated (arrow). The numbers above each tracing indicate the rate of oxygen consumption (nmol/min/mg). (b) Effect of doxorubicin on oxygen consumption by Ehrlich tumor mitochondria. Oxygen consumption in these representative experiments was performed as described in Supplementary Table 2. (i) is the control reaction; (ii) represents the identical experiment in the presence of doxorubicin (135 μM). The addition of catalase (4500 units) to the 3 ml vessel was performed through the access slot of the oxygen electrode and has been indicated by the arrow. The numbers above each tracing indicate the rate of oxygen consumption (nmol/min/mg). (c) Effect of doxorubicin on oxygen consumption by Ehrlich tumor nuclei. Experimental conditions consisted of a 3 ml system containing 250 mM sucrose, 20 mM HEPES, pH 7.4, 100 μM EDTA, 1 mM NADPH, and 200 μg/ml of nuclear protein at 37°C. The addition of NADPH (1 mM), doxorubicin (135 μM), or catalase (4500 units) to the 3 ml reaction vessel was performed through the access slot of the oxygen electrode and has been indicated by an arrow. The number above the tracing is the rate of oxygen consumption (nmol/min/mg). (d) Doxorubicin-stimulated oxygen consumption by Ehrlich tumor cells. The effect of doxorubicin (400 μM) on oxygen consumption by Ehrlich cells ( cells/ml) is shown in representative examples from multiple experiments. The addition of acetylated cytochrome c (168 nmol) in (i) or catalase (9000 units) in (ii) to the 3 ml vessel has been indicated by an arrow. The numbers above each tracing indicate the rate of oxygen consumption (nmol/min/ml).

(a)

(b)

(c)

(d)