Mitochondrial damage and inhibition of respiration in animal cell cultures treated with Triton WR‐1339

Inhibition of cellular respiration by treatment with the nonionic detergent Triton WR‐1339 was found to be related to the cytotoxic response of cell to the surfactant. Respiration of sensitive cell lines (AV‐3 and HeLa) markedly inhibited by Triton concentrations as low as 125 μgm/ml. Conditionally sensitive lines (BHK‐21 and L‐929) were affected by 500 μgm/ml while the respiration of insensitive cultures (primary rat and chick embryo cells) was unaffected by this concentration. Macrocyclon, a cyclic analogue of Triton, failed to alter the respiration rate of any of the above cell cultures. The levels of isocitric and succinic dehydrogenases in sensitive and conditionally sensitive cells were depressed within 2 hours after treatment with 500 μgm/ml of Triton was initiated and by 6 hours the activity was only 25% of the untreated controls. Similar results were obtained with mitochondrial preparations from these cells. Enzyme levels in insensitive cells were unaffected by Triton treatment. Mitochondrial damage was the most striking characteristic noted in treated cells examined by electron microscopy. The mitochondria were quite distorted and had lost most of their cristae formation. This mitochondrial damage was seen in all cell types examined although the rate at which it occurred varied. With sensitive cultures, damage was pronounced within 6 hours after the addition of Triton while mitochondria from conditionally sensitive cells were not grossly affected until 48 hours and they appeared to repair the damage following the removal of Triton.