Ammonium chloride-induced alterations in growth kinetics and ultrastructure of murine neuroblastoma cells. A flow cytometric and stereologic study.

Neuro-2a and L-132 cells have been used as a model in the study of ammonia toxicity. Incubation of neuro-2a cells for 48 h in the presence of 2 mM NH4Cl caused inhibition of their growth and accumulation of cells in the G2M phase of the cell cycle as demonstrated by fluorocytometric methods. Mitotic figures were absent in the treated cell preparations. On the other hand, ammonia had no effect on L-132 cells treated in the same way. Electron microscopy of neuro-2a cells incubated with 2 mM NH4Cl for 5 days showed striking qualitative and quantitative ultrastructural changes compared with control cells. Treated cells doubled in absolute volume and showed marked alterations in the shape and organization of mitochondria. The absolute volume of mitochondria was also increased which, together with a decrease in their total number, suggests that ammonia induces fusion between adjacent mitochondria. Increases in the total number of lysosomes, multivesicular bodies and lipid droplets were also found in treated cells.