Induction of complete and irreversible damage to malignant glioma cells by L-2,4 diaminobutyric acid.
L-2,4 Diaminobutyric acid (DAB), a non-physiological amino acid, induced an irreversible injury to human malignant glioma cells when incubated for 24h at an amino acid concentration of 6 mmol/l at 37 degrees C. The same treatment of the human glia cells did not result in any cellular damage; not even a concentration as high as 20 mmol/l of the amino acid under the same incubation conditions did affect these cells. However, a further increase in amino acid concentration above that level resulted in a gradual loss of viability among the human glia cells. An experimentally induced rat glioma cell line was also affected by DAB, although displaying less sensitivity than the human glioma cells, and complete cellular destruction was achieved at 16 mmol/l of DAB, i.e. well below the critical concentration for human glia cells. The destructive effect by DAB was pH-sensitive. The N-methylated analogue of a - amino-isobutyric acid exerted a specific inhibitory action on DAB activity, but other amino acids were also inhibitory to various degrees at higher concentrations. Future clinical applications in the treatment of malignant brain tumours in man are discussed.
D000613:Aminobutyrates / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051381:Rats; D013045:Species Specificity
D000613:Aminobutyrates; D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; C005959:2,4-diaminobutyric acid