Inhibitory action of orotate, 2-thioorotate and isoorotate on nucleotide metabolism and nucleic acid synthesis in hepatoma cells.
1. The specificity of the action of orotate on hepatoma cells was investigated. 2. Orotic acid and its methyl ester had similar inhibitory effects on the incorporation of [3H]thymidine into DNA of hepatoma cells. 3. In contrast to previous studies in vivo, incubation of rat kidney cells with orotate caused an increase in the ratio of UTP/ATP concentrations that was similar to effects on hepatic cells. 4. Inhibitory effects of 2-thioorotate and isoorotate on metabolism were found to be less selective and required higher concentrations than with orotate.
Lea
M A
MA
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
Luke
A
A
Assad
A
A
Patel
M
M
Reddy
P A
PA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D009963:Orotic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009711:Nucleotides; D009963:Orotic Acid