COMPARISON OF CELL-PROLIFERATION FOLLOWING PARTIAL-HEPATECTOMY IN RATS FED NIH-31 OR SEMIPURIFIED AIN-76A DIETS - EFFECTS OF NUCLEIC-ACID SUPPLEMENTATION

Male Fischer 344 rats, were administered NIH-31, AIN-76A, or AIN-76A p lus 0.25% yeast RNA diets for 3 weeks, partially hepatectomized (PH), and groups of 6 rats from each diet group were sacrificed at 0, 2, 7 a nd 14 days following PH. Liver weight, total DNA, total lipids, levels of thiobarbaturic acid reactive substances (TEARS), and levels of int racellular deoxyribonucleotides were determined. In addition, the numb er of hepatocytes in mitosis and/or positive for nuclear proliferating cell nuclear antigen (PCNA) were determined. Liver regeneration, meas ured as liver weight or total liver DNA, was equal in the three diet g roups and was essentially complete by the end of 14 days. However, the re was a 53% reduction in the mitotic index and a two-fold increase in the ratio of proliferating cells (G1 + S + G2 cells) to mitoses at 48 hours in animals of the AIN-76A diet group compared to those fed NIH- 31 diet, suggesting that the cells were arrested or delayed in S-phase . At the time of PH, liver deoxyuridine monophosphate (dUMP) and deoxy thymidine triphosphate (dTTP) levels in the AIN-76A group were decreas ed 29% and 57%, respectively, compared to those of the NIH-31 group. A ddition of yeast RNA to the AIN-76A diet partially prevented the decre ase in mitosis and maintained deoxyribonucleotide triphosphates (dNTP) levels to those of the NIH-31 group. These results indicate that the lack of dietary nucleotides in semipurified diets can alter dNTP level s and have adverse effects on cell proliferation. Consideration should be given to supplementing purified diets with a dietary source of nuc leotides.