Abstract
The present study was designed to determine the mechanism by which orotic acid, a rat liver tumor promoter, inhibits DNA synthesis in normal hepatocytes in primary culture. Our results indicate that orotic acid inhibited the epidermal growth factor induced expression (mRNA) of both M1 and M2 subunits of ribonucleotide reductase while the expression of c-fos, c-myc, c-Ha-ras and beta-actin was not inhibited to any significant extent. These studies suggest that ribonucleotide reductase may be one target for orotic acid-induced mitoinhibition.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenosine Triphosphate / metabolism
-
Animals
-
Antineoplastic Agents / pharmacology*
-
Blotting, Northern
-
Cell Cycle / physiology
-
Cells, Cultured
-
DNA / biosynthesis
-
Epidermal Growth Factor / antagonists & inhibitors
-
Epidermal Growth Factor / pharmacology
-
Gene Expression / drug effects
-
Liver / cytology
-
Liver / drug effects*
-
Liver / enzymology*
-
Macromolecular Substances
-
Male
-
Orotic Acid / pharmacology*
-
Rats
-
Rats, Inbred Strains
-
Ribonucleotide Reductases / antagonists & inhibitors*
-
S Phase / physiology
-
Uracil Nucleotides / metabolism
Substances
-
Antineoplastic Agents
-
Macromolecular Substances
-
Uracil Nucleotides
-
Orotic Acid
-
Epidermal Growth Factor
-
Adenosine Triphosphate
-
DNA
-
Ribonucleotide Reductases