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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
Arsenate, an uncoupler of oxidative phosphorylation, relieved the Crabtree effect in Ehrlich-Lettré hyperdiploid ascites tumor cells. Respiration was measured with an oxygen electrode. High arsenate concentrations (30 to 60 mM) were needed to produce a 2-fold increase in the depressed respiratory rate. Arsenate concentrations below 10 mM had little or no effect. The relief by arsenate was reversible with oligomycin, indicating that arsenate had not caused a nonspecific uncoupling. A comparison of the effects of arsenate on oxidative phosphorylation in isolated Ehrlich-Lettré hyperdiploid ascites tumor mitochondria and on the onset of the Crabtree effect in intact Ehrlich-Lettré hyperdiploid ascites tumor cells suggested that the high arsenate concentrations were needed to overcome a strong antagonism by inorganic phosphate for the arsenate uncoupling. The results support the concept that the Crabtree effect is caused by a decrease in the availability of ADP and/or inorganic phosphate to oxidative phosphorylation.
1 Supported in part by USPHS Grant 059540-07. A portion of this work was done while the author was at the Rockefeller University, New York, N. Y.
Received 9/12/69. Accepted 1/ 9/70.
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