Evoke rRNA Cleavages Lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria that can activate macrophages via the Toll-like receptor 4 receptor, did not affect rRNA integrity indicating that the macrophage activation per se was insufficient to induce RNA cleavage. Because DON is a translational inhibitor and causes rRNA cleavage indirectly, we questioned whether this might be a common effect for other ribotoxins. Cells were incubated with SG and anisomycin, which can freely diffuse through cell membrane and ricin, a RIP, which can enter the cells by endocytosis and retrograde translocation to ER and cytosol. Unlike SG and anisomycin that directly bind to ribosome to inhibit translation, ricin possesses inherent RNA N-glycosidase activity to depurinate RNA. Although these toxins have apparently different mechanisms for inhibiting translation, SG, anisomycin, and ricin induced a similar apoptosis-mediated cleavage profile to that of DON (Fig. 8) , suggesting that ribotoxins might share conserved pathway for mediating rRNA cleavage. 