Abstract
Summary
The in vivo and in vitro effects of the carcinogen dimethylnitrosamine (DMN) on the metabolic activity of mitochondria were studied. Oxygen consumption by mitochondria in state 3 and state 4 was determined polarographically following the addition of succinate or glutamate as substrates. The control of respiration by ADP is indicated by the ratio of state 3 to state 4 oxygen utilization (RCR), and is indicative of the tightness of coupling of the oxidative phosphorylation and electron transport systems. DMN in concentrations of 37.8 μM and higher significantly decreased state 3 oxidation of glutamate. State 4 oxidation of glutamate was inhibited significantly only at DMN concentrations of 75, 151, and 226 μM (5, 10, and 15 μg! ml). The RCR was decreased corresponding to the decrease in state 3 oxidation. Similar results, but to a lesser magnitude, were obtained using succinate as substrate. In mitochondria from mice treated with DMN (25 mg/kg ip) state 3 oxygen consumption was decreased and the RCR was significantly different from control with either substrate. The results indicate that DMN inhibits oxidative phosphorylation both in vivo and in vitro.
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