Differential cell cycle perturbation by transmethylation inhibitors

Cell cycle distribution of HL-60 cells was studied by flow cytometry after incubation with the transmethylation inhibitors 3-deaza-(±)-aristeromycin (c 3Ari) and 3-deazaadenosine (c 3Ado). Cells were incubated with the drugs (25 μM) for two cell doublings in control cells (36 hr). The presence of c 3Ari caused a dose-dependent, reversible G 2+M arrest, whereas c 3Ado-treated cells accumulated in G 0/G 1,. The G 2+M arrest was also found in NIH/3T3 cells incubated for 36 hr with 25μM c 3Ari, but not in U937 and K562 cells. Possible mechanisms for the described effects of c 3Ari are discussed from the perspective that inhibition of S-adenosyl homocysteine hydrolase, and subsequent inhibition of transmethylation reactions, at present is the only known site of action of c 3Ari.