THE EFFECT OF CARBON MONOXIDE ON OXYGEN CONSUMPTION, GLUCOSE UTILIZATION, AND GROWTH IN MAMMALIAN CELLS IN VITRO

The effect of carbon monoxide on respiration, growth, and carbohydrate metabolism of Earle's L strain cells was investigated. The rate of gas uptake by suspensions of cells in a Warburg respirometer was the same from mixtures containing various proportions of CO/O2/N2 or containing only O2/N2. Apparently carbon monoxide was not inhibiting oxygen consumption. In respirometers filled with carbon monoxide and oxygen in the ratio of 9:1, illumination caused the net gas uptake to rise 23% above that of the controls. This suggests that the rate of oxygen consumption in the dark was reduced as a consequence of an inhibition of a respiratory enzyme by carbon monoxide. In keeping with this suggestion, a spectroscopic examination revealed the presence in L cells of absorption bands corresponding to those of the cytochrome enzymes. Using differential manometers it was established for the first time that carbon monoxide is taken up by L cells in the dark. It is concluded that a fraction of the gas uptake which is represented by the consumption of oxygen associated with normal metabolism must be reduced in the presence of carbon monoxide. It is also concluded that L cells oxidize carbon monoxide to carbon dioxide. The rate of multiplication of cells was reduced by carbon monoxide while the rate of glucose breakdown and lactic acid production were markedly accelerated, suggesting that there was an inhibition of cytochrome oxidase. Low partial pressures of oxygen also reduced the rate of multiplication of L cells while increasing the rate of glucose disappearance and the rate of lactic acid production. The observations reported here thus emphasize the role of aerobic oxidations in the maintenance of the maximum rate of growth.