DIETARY NUCLEOTIDES - EFFECTS ON CELL-PROLIFERATION FOLLOWING PARTIAL-HEPATECTOMY IN RATS FED NIH-31, AIN-76A, OR FOLATE METHYL-DEFICIENT DIETS/

The requirement of a number of tissues for dietary nucleotides could e xplain some of the differences observed in animals fed natural ingredi ent diets vs. those fed purified diets lacking a source of dietary nuc leotides. Lack of dietary nucleotides is exacerbated in animals fed fo late- or methyl-deficient semipurified diets, in which both salvage an d folate-dependent de novo synthetic pathways are diminished. We exami ned hepatocyte proliferation following partial hepatectomy in weanling male Fischer-344 rats fed natural ingredient NIH-31 diet, nucleotide- free purified AIN-76A diet or a basal diet similar to AIN-76A but defi cient in the methyl donors folate, choline and methionine. Additional groups were fed AIN-76A or folate/methyl-deficient diets supplemented with 0.25% yeast RNA. Compared with NIH-31,AIN-76A increased dUMP/dTTP ratios, reduced the mitotic index (MI) and increased the ratio of pro liferating cell index (PCI) to mitotic cells, an indication that hepat ocytes were delayed in S-phase. Addition of yeast RNA to AIN-76A rever sed (by approximately 50%) the effects of AIN-76A on dUMP/dTTP and cel l proliferation. A folate/methyl-deficient diet also produced an incre ased dUMP/dTTP ratio and markedly reduced the MI, increasing the PCI/M I, which suggested even further delay of cells in S-phase. Addition of yeast RNA to the folate/methyl-deficient diet was effective in signif icantly reversing the effects of folate/methyl deficiency.