EFFECTS OF SPIN-LABELED DERIVATIVES OF PODOPHYLLOTOXIN ON CELL-CYCLE AND MACROMOLECULAR-SYNTHESIS IN HUMAN LYMPHOID LEUKEMIA MOLT 4B CELLS

AIM: To examine the effect of the spin labeled derivatives of podophyl lotoxin, N-podophyllic acid-N ''-[4-(2, 2, 6, 6-tetramethyl-1-piperidi nyloxy)] thiosemicarbazide (GP4) and 4-[4 ''-(2 '', 2 '',6 '', 6 ''-te tramethyl-1 ''-piperidinyloxy) amino]4'-demethylepipodophyllotoxin (GP 7) on the cell cycle and macromolecular synthesis of human lymphoid le ukemia Molt 4B cells in vitro. METHODS: MTT assay, H-3 incorporation, and now cytometer were used. RESULTS: GP4, GP7, and etoposide 0.02 - 1 00 mmol . L-1 cultured for 48 h inhibited the proliferation of human l ymphoid leukemia Molt 4B cells. IC50 values of GP4, GP7, and etoposide were 0.11, 4.7, and 1.6 mmol . L-1, respectively. DNA and protein syn theses were obviously suppressed by GP4, GP7, and etoposide 10 mmol . L-1 for 48 h. After Molt 4B cells were treated with GP4, GP7, and etop oside 10 mmol L-l for 6 and 12 h, the mitotic index was increased by G P4 and reduced by GP7 and etoposide. According to now cytometric BrdU/ DNA analysis, GP4 slightly retarded S phase and mainly arrested cell c ycle progression in G(2)/M phase, whereas GP7 similar to etoposide ind uced cells accumulated at S phase and retarded the cells in Ci phase. CONCLUSION: GP4 and GP7 inhibit the proliferation of Molt 4B cells, bu t the mechanisms are different.