AN ADDITIONAL MECHANISM OF RIBOSOME-INACTIVATING PROTEIN CYTOTOXICITY- DEGRADATION OF EXTRACHROMOSOMAL DNA

Inhibition of protein synthesis by cleavage of the N-glycosidic bond o f a specific adenine of 28 S rRNA has been accepted as the mechanism b y which plant ribosome-inactivating proteins (RIPs) cause cytotoxicity . The cytotoxic action of gelonin on Plasmodium falciparum malaria par asites appears to occur by a different mechanism. Parasite intoxicatio n, which is manifested by mitochondrial dysfunction and lack of nuclei c acid synthesis in the erythrocytic cycle following exposure to the t oxin, is caused by the elimination of the parasite 6 kb extrachromosom al (mitochondrial) DNA. This is the first report which demonstrates th at the DNA-damaging activities of RIPs observed in vitro can contribut e to their cytotoxicity.