Effects of Dietary Feeding of Aflatoxin B₁on Ribosomal RNA Metabolism in Rat Liver

After 1 week of dietary feeding of Aflatoxin B₁(AFB,) (1 or 10 ppm) to male Fischer rats, sucrose gradient analysis revealed decreases in the incorporation of [³H]orotic acid in vivo into 45 S hepatic nRNA and decreased concentration (A260 of 28 S nRNA when compared with controls fed an identical diet minus AFB₁. Sucrose gradient analysis of hepatic microsomal rRNA showed decreases of a similar magnitude in labeling in vivo and in A₂₆₀of 28 S rRNA. Labeling and A₂₆₀of the 18 S rRNA were unchanged. Assay of RNA polymerase I activity in isolated hepatic nuclei demonstrated that this enzyme activity was not diminished in rats fed the AFB, diet from that of the controls. Feeding of AFB₁for 1 to 6 weeks resulted in progressive decreases in A₂₆₀of 28 S nRNA and in both label and A₂₆₀in microsomal 28 S rRNA. These effects are time and dose related, since 1 week of a diet containing 10 ppm produced changes in nuclear and ribosomal 28 S RNA similar to those observed after 4 to 6 weeks of a diet containing 1 ppm. Sixteen hr after a single injection of AFB, (1 mg/kg i.p.), the same defects in RNA metabolism occurred as described above for 1 ppm for 4 to 6 weeks and 10 ppm for 1 week. In contrast to the chronic feeding studies, after an acute injection these effects eventually disappear. These data suggest that early progressive lesions in the maturation of hepatic 28 S rRNA are produced during chronic feeding of a diet containing AFB,. Such defects in processing of ribosomal precursor RNA may be a characteristic feature of chemical hepatocarcinogenesis.