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 (c3 Ari) and 3-deazaadenosine (c3 Ado). Cells were incubated with the drugs (25 microM) for two cell doublings in control cells (36 hr). The presence of c3 Ari caused a dose-dependent, reversible G2 + M arrest, whereas c3 Ado-treated cells accumulated in G0/G1. The G2 + M arrest was also found in NIH/3T3 cells incubated for 36 hr with 25 microM c3 Ari, but not in U937 and K562 cells. Possible mechanisms for the described effects of c3 Ari 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 c3 Ari.