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PolyADP ribosylation and Friend erythroleukemic-cell differentiation: action of poly(ADP-ribose) polymerase inhibitors.

Previous studies have shown that benzamide and nicotinamide, two inhibitors of poly(ADP-ribose) polymerase, induce erythroid differentiation in Friend erythroleukemic cells. In contrast, we observed that two other commonly used inhibitors, i.e., 3-aminobenzamide and 3-methoxybenzamide, not merely failed to induce differentiation but actually inhibited it. Furthermore, we observed that benzamide at high concentrations induced differentiation, whereas at low concentrations, it inhibited differentiation. We propose that the induction occurring at high concentrations is due to the polar-planar properties of the molecule, while the inhibition at low concentrations might be due to the inhibition of poly(ADP-ribose) polymerase. Cells that were first exposed to an inducer (hexamethylene bisacetamide) and an inhibitor (3-aminobenzamide) and were subsequently incubated in medium lacking these substances did not differentiate. However, re-exposure to the inducer resulted in a very rapid increase in commitment to terminal differentiation. Therefore, 3-aminobenzamide appears to block differentiation prior to the commitment stage. We infer from these findings that polyADP-ribosylation is required for the terminal differentiation of Friend erythroleukemia cells.