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 explain some of the differences observed in animals fed natural ingredient diets vs. those fed purified diets lacking a source of dietary nucleotides. Lack of dietary nucleotides is exacerbated in animals fed folate- or methyl-deficient semipurified diets, in which both salvage and folate-dependent de novo synthetic pathways are diminished. We examined 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 deficient 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 proliferating cell index (PCI) to mitotic cells, an indication that hepatocytes were delayed in S-phase. Addition of yeast RNA to AIN-76A reversed (by approximately 50%) the effects of AIN-76A on dUMP/dTTP and cell proliferation. A folate/methyl-deficient diet also produced an increased dUMP/dTTP ratio and markedly reduced the MI, increasing the PCI/MI, which suggested even further delay of cells in S-phase. Addition of yeast RNA to the folate/methyl-deficient diet was effective in significantly reversing the effects of folate/methyl deficiency.
Jackson
C D
CD
Division of Nutritional Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Weis
C
C
Miller
B J
BJ
James
S J
SJ
D000821:Animal Feed; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D003854:Deoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D003856:Deoxyuracil Nucleotides / Q000494:pharmacology; D004032:Diet; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency; D005526:Food, Formulated; D006498:Hepatectomy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013942:Thymine Nucleotides / Q000494:pharmacology; D014886:Weaning
D003854:Deoxyribonucleotides; D003856:Deoxyuracil Nucleotides; D013942:Thymine Nucleotides; D005492:Folic Acid; C007267:2'-deoxyuridylic acid; C024157:thymidine 5'-triphosphate