PREVENTION OF S-D-LACTOYLGLUTATHIONE-INDUCED INHIBITION OF HUMAN LEUKEMIA-60 CELL-GROWTH BY URIDINE

The anti-proliferative activity of S-D-lactoylglutathione is of intere st since it has a low toxicity to differentiated and non-malignant pro liferating tissues, and its mechanism of action appears to be dissimil ar to other anti-proliferative agents. Addition of uridine completely and addition of cytidine partially prevented S-D-lactoylglutathione-in duced growth inhibition of human leukaemia 60 (HL60) cells in vitro. O ther nucleosides had no significant effect. The concentrations of UTP, CTP, UDP and also ATP, ADP, GTP and GDP decreased in S-D-lactoylgluta thione-treated HL60 cells, whereas the concentration of UDP-N-acetylhe xosamine (UDP-N-acetyl-glucosamine + N-acetyl-galactosamine) increased , prior to cell death. This suggests that the anti-proliferative effec ts of S-D-lactoylglutathione are mediated by inhibition of uridylate s ynthesis.