Evaluation of possible sites of action of rubratoxin B-induced polyribosomal disaggregation in mouse liver.
The disaggregation of liver polyribosomes (disruption of the site of protein synthesis) into single ribosomal units has been observed after treatment of mice with rubratoxin B, a toxic metabolite of Penicillium rubrum. Several mechanisms for the polysomal alteration were evaluated. A generalized decrease in mouse liver RNA following administration of rubratoxin B was noted. RNAase activity in the postmicrosomal fraction was increased after similar treatment; however, this increase was too small to account for the observed polysomal breakdown. Incubation of rubratoxin B with isolated polysome fractions indicated no direct interaction between the toxin and the polyribosomal complex, apparently eliminating such a complex as the cause of the in vivo disaggregation. Rubratoxin caused shifts in the ultraviolet absorption spectra of DNA and RNA in vitro, a preliminary indication of binding of the toxin to nucleic acid. Such preliminary observations lend support to the hypothesis that rubratoxin-induced polyribosomal disaggregation may result from an alteration in the critical informational macromolecules such as nucleic acids, or protein, or both in that both are involved in the control of cell growth. This alteration in the DNA-protein complex may then result in a malfunction of the DNA-dependent RNA polymerase activity and subsequent polysomal disaggregation.
D000818:Animals; D004247:DNA / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000648:ultrastructure*; D051379:Mice; D008813:Mice, Inbred ICR; D009183:Mycotoxins / Q000494:pharmacology*; D011132:Polyribosomes / Q000187:drug effects* / Q000201:enzymology; D012313:RNA / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
D009183:Mycotoxins; D012313:RNA; D004247:DNA; D012260:Ribonucleases