Differential sensitivity of tumor cells to externally generated hydrogen peroxide. Role of glutathione and related enzymes.

(1) Oxygen uptake and lactate production of different strains of ascites tumor cells were assayed after exposure to an extracellular photochemical system known to produce reactive oxygen derivatives. The various cells tested showed differential sensitivity to the treatment, ranging from nearly full inactivation of Ehrlich cells to nearly full resistance of Yoshida cells. (2) Glucose plus succinate added after the treatment reestablished basal oxygen uptake capacity suggesting that the cell membrane was the primary site of damage. This was confirmed by dye-permeabilization and protein leakage in sensitive cells. (3) H2O2 was shown to be the only relevant oxygen derivative in the production of cell damage: catalase was the only externally added agent that protected sensitive cells, and H2O2 (congruent to 10(-3) M) had the same effects as the photochemical treatment. (4) While the absence of catalase is a feature common to all tumors tested, sensitivity to H2O2 appears to be related to cellular levels of glutathione peroxidase and of its subsidiary enzymes glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione synthetase.