ANTAGONISM BY L-GLUTAMINE OF TOXICITY AND GROWTH-INHIBITION CAUSED BYOTHER AMINO-ACIDS IN SUSPENSION-CULTURES OF NICOTIANA-SILVESTRIS

The toxicity of L-amino acids toward exponentially dividing cells of N icotiana silvestris in suspension culture was monitored by following g rowth rates throughout a span of 8 days. Except for L-glutamine, all 1 9 protein amino acids inhibited cell growth. Inhibition progressed wit h an initial stage of slowed exponential growth. Cells in this stage w ere receptive to complete recovery under some conditions. Otherwise an irreversible stage of total growth inhibition and progressive cell de terioration followed. Electron microscopy showed that amino acids trig gered a state of cell shrinkage which eventually degenerated to total cellular disorganization. An apparent exocytotic deposition of condens ed and blackened cellular debris occurred between the cell wall and pl asmalemma. L-Glutamine was not only an effective agent for prevention of amino acid toxicity, but enhanced the final growth yield. L-Glutami ne also was able to completely reverse inhibitor effects in cells whic h had been in the slowed exponential phase for up to 3 days. We propos e that any amino acid inhibition which can be completely antagonized b y L-glutamine be called 'general amino acid inhibition'. 'Specific ami no acid inhibition', resulting from particular pathway imbalances caus ed by certain exogenous amino acids, can be recognized and studied in the presence of L-glutamine which abolishes the complicating effects o f general amino acid inhibition. It is hypothesized that the L-glutami ne:amino-acid ratio established in vivo might influence susceptibility to apoptosis, a eukaryotic process of programmed cell death which has been characterized most extensively in animals.