A prominent consequence of DON exposure in macrophages is ribosomal RNA (rRNA) cleavage, which could negatively impact innate immune function (Li and Pestka, 2008) . Two fundamental questions arising from this work relate to the specificity and mechanisms for this cleavage. Using oligonucleotide extension, we identified one site of DON-induced rRNA cleavage is within the peptidyl transferase center of 28S rRNA; however, further identification of additional sites was precluded by the relatively poor resolution of conventional gel electrophoresis and limitations on this techniques imposed by RNA hairpin structures (Li and Pestka, 2008) . Regarding mechanisms, it is known that ricin and other ribosomeinactivating proteins (RIPs) cleave rRNA via a highly specific mechanism that involves N-glycosidase-mediated adenine depurination at highly conserved sarin/ricin (S/R) loop (Endo and Tsurugi, 1986; Hartley and Lord, 2004) . However, DON and other trichothecenes are low molecular weight chemicals and are devoid of inherent enzyme activities (Li and Pestka, 2008) . Induction of rRNA cleavage by chemicals or viruses has previously been suggested to be linked to apoptosis (Banerjee et al., 2000; Naito et al., 2009) raising the possibility that DONinduced rRNA cleavage might be similarly linked to this mechanism of cell death.