Unique antitumour effects of L-2,4 diaminobutyric acid on cultured hepatoma cells.

A single hepatoma cell line was grown in vitro and incubated with L-2,4 diaminobutyric acid (DAB), a non-metabolizable amino acid, under various conditions. The tumour cells were irreversibly damaged by incubation for 8 hours with 8 mmol/L of DAB. The tumour cell-destroying effect of DAB was dose- and time-dependent with no effect at a DAB concentration of 1.6 mmol/L. The presence of N-methyl alpha-aminoisobutyric acid (a specific substrate of amino acid transport system A) in the incubation medium abrogated the tumour cell destructive effect of DAB in a dose-dependent fashion. The presence of non-physiological amino acids in the incubation medium per se was not the cause of tumour cell destruction, since inclusion of alpha-amino-isobutyric acid and N-methyl alpha-aminoisobutyric acid in the incubation medium did not influence the viability of hepatoma cells. We conclude that the tumour cell destructive effect of DAB was the result of a huge and unlimited uptake of DAB energized by the Na(+)-gradient and that this uptake was not subjected to the law of saturation kinetics. This was combined with a tumour cell energy crisis in attempts to restore the Na(+)-gradient.