The Effect of Diphtheria Toxin on the Metabolism of Hela Cells

The effect of diphtheria toxin on certain metabolic processes in growing HeLa cells has been described. It was found that both aerobic respiration and glycolysis are insensitive to toxin action. The incorporation of S(35)-methionine was found to be completely inhibited by toxin prior to the appearance of any visible cell damage. It was also observed that toxin levels above 0.3 Lf per ml. had no further effect on the kinetics of inhibition of methionine uptake. The kinetics of intoxication were studied by adding diphtheria antitoxin to a partially intoxicated culture at various times and measuring the resulting rate of methionine uptake. Low temperatures were found to block intoxication. Using this information, data were obtained suggesting that the initial step in the process of intoxication consists of a rapid adsorption of toxin by the cell. The kinetics of toxin action on protein synthesis were compared with those of cyanide and 2,4-DNP. Diphtheria toxin eliminates completely any methionine uptake remaining after exposure of the cell to either of these respiratory inhibitors. The significance of these results is discussed.