The effect of 2, 4-dinitrophenol and of fluoride on oxidations in normal and tumor tissues.

INTRODUCTION Earlier work from this laboratory (9, 11) has shown that the addition of fluoride permits isotonic homogenates of the Walker 256 carcinosarcoma and the Flexner-Jobling carcinoma to oxidize to an appreciable extent the various inter mediates of the tricarboxylic acid cycle when sup plemented with adenosinetriphosphate (ATP). From data on phosphate balance (11, 12), it has been suggested that the oxidative level is affected by the balance between high-energy phosphate breakdown and the uptake of inorganic phosphate into organic form. Thus, in the tumors where phos phate breakdown is very high, fluoride acts to pre serve the respiratory rate by inhibiting the break down of high-energy phosphate (9, 11). Since the homogenates of several normal tissues do not need the addition of fluoride to demonstrate oxidation (8, 11, 12), it was thought worth while to investi gate other tumors than those mentioned to observe whether the behavior in the presence of fluoride is characteristic of all tumor tissue. Since it has been shown that 2,4-dinitrophenol (DNP) acts to stimulate the breakdown of highenergy phosphate (2, 4, 13), the present work was concerned with whether DNP further decreases the low oxidation rate in those tissue homogenates in which there is a stimulation by fluoride and whether it increases the oxidation of those tissue homogenates in which there is no effect by fluoride or where fluoride is inhibitory. In general, DNP and fluoride have been found to act somewhat an tagonistically with respect to their effects on oxi dation. Thus, the behavior of a homogenate of a tissue in the presence of DNP and of fluoride will roughly characterize that tissue as to its ability to break down high-energy phosphate and as to the ability of its oxidative phosphorylation mechanism to keep pace with this breakdown.