SELECTIVE CYTOTOXICITY OF L-GLUTAMIC ACID GAMMA-MONOHYDROXAMATE (GAH)FOR MELANOMA TUMOR-CELLS

We have previously shown that L - glutamic acid gamma-monohydroxammate (GAH) exhibits an antitumor activity, both in vitro and in vivo. In t his report we explore the selective cytotoxicity of GAH in vitro by co mparing the survival of tumor and normal cells. GAH exerts an irrevers ible delayed effect with tumoral cells and a reversible effect with no rmal cells. after a short incubation time of 6 hrs in the presence of 1.2 mM GAH and after removal of the drug, the survival of N Ter Dau an d MRC5 cells was identical reaching about 85% after 24 hrs of culture. But, after another 48 hrs of culture, MRC5 cells recovered 100% cell survival while with N Ter Dau cells the survival decreased to 65%. A l onger exposure time to GAH (18 hrs) and an additional 54 hrs of cultur e after removal of GAH led to 50 +/- 10% of cell survival with normal cells but only 25 +/- 10% with tumor cells. Using a long - term clonog enic assay, we showed that the 25% N Ter Dau cells surviving at 72 hrs after GAH treatment led mainly to abortive colonies (17% +/- 3%) with only 2.3 +/- 0.9% of surviving colonies. Such a difference does not e xist for normal cells. Cell cycle analysis of tumor and normal cells t reated with GAH (18 hrs, 1, 2 mM) has shown that the drug prevents bot h cell type from cycling from G1 to S phase. However, the two cell typ es started to cycle again after removal of GAH but a delay of 24 hrs w as observed for tumoral cells compared-to normal cells.