Dietary orotic acid, a new selective growth stimulus for carcinogen altered hepatocytes in rat.
It was observed that orotic acid (OA), a precursor for pyrimidine nucleotide biosynthesis, when supplied exogenously at 1% level in the diet selectively stimulated the growth of hepatocytes modified by 1,2-dimethylhydrazine (1,2-DMH) to form gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) positive islands. Increasing the duration of OA diet from 5 to 10 weeks resulted in an increase in the number of foci from 6 to 14/cm2. Rats that received the carcinogen and basal diet, however, developed only 1-2 foci/cm2. This unique effect of OA can be further accentuated by supplying a liver cell proliferative stimulus, such as a single necrogenic dose of CCl4.
D000821:Animal Feed; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D004127:Dimethylhydrazines / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009963:Orotic Acid / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000032:analysis
D002273:Carcinogens; D004127:Dimethylhydrazines; D009963:Orotic Acid; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase