The effects of prolonged feeding with aflatoxin B1 on adult rat liver.

The effects of feeding adult rats for 6 weeks with a carcinogenic regimen of aflatoxin-contaminated diet are described. Effects on the histological appearance of liver sections are related to changes observed in nuclear separations carried out using zonal centrifugation. Changes in the levels of nuclear RNA and DNA synthesis have been studied in the populations of hepatic nuclei separated in the zonal rotor. The first 3 weeks of the feeding period was accompanied by continuing inhibitions of nucleic acid synthesis, terminating in a loss of the majority of the tetraploid hepatocyte nuclear population. The subsequent 3 weeks of feeding was predominantly a period of proliferation, restoration of the lobular architecture, and recovery of nucleic acid-synthetic activity. The possible bases of these two opposite effects, inhibition followed by stimulation, which occurred sequentially during the continued feeding of the toxic diet, are discussed.