Biomaterial Database

Decreased fidelity of DNA polymerase activity during N-2-fluorenylacetamide hepatocarcinogenesis. 1979

J Y Chan, and F F Becker

alpha and beta DNA polymerases (DNA nucleotidyltransferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7) were isolated from nuclear and cytoplasmic fractions of rat livers exposed to a carcinogenic regimen with the hepatocarcinogen N-2-fluorenylacetamide and from 24-hr regenerating liver. The fidelity of polymerization of these enzymes was compared by determining the incorporation of noncomplementary deoxyribonucleoside triphosphates (misincorporation) on a poly(dA-dT).poly(dA-dT) template, with MnCl2 and MgCl2 as divalent cations. Our initial studies indicate that the cytoplasmic alpha polymerases from carcinogen-exposed rat livers were strikingly error-prone whereas the nuclear and cytoplasmic beta polymerases retained their fidelity throughout the feeding cycles. The misincorporation was significantly accentuated by MnCl2 compared with that obtained with MgCl2 as divalent cation. The products were sensitive to pancreatic DNase I digestion, indicating that the noncomplementary bases had been incorporated by the polymerization process. Nuclear alpha polymerase showed some degree of infidelity but less than that of cytoplasmic alpha polymerase.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008114	Liver Neoplasms, Experimental	Experimentally induced tumors of the LIVER.	Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008115	Liver Regeneration	Repair or renewal of hepatic tissue.	Liver Regenerations,Regeneration, Liver,Regenerations, Liver
D008274	Magnesium	A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008297	Male		Males
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D011067	Poly dA-dT	Polydeoxyribonucleotides made up of deoxyadenine nucleotides and thymine nucleotides. Present in DNA preparations isolated from crab species. Synthetic preparations have been used extensively in the study of DNA.	Poly(Deoxyadenylate-Thymidylate),Polydeoxyadenine Nucleotides-Polythymine Nucleotides,Poly dA dT,Poly(dA-dT),d(A(5)T(5))2,Nucleotides, Polydeoxyadenine Nucleotides-Polythymine,Nucleotides-Polythymine Nucleotides, Polydeoxyadenine,Polydeoxyadenine Nucleotides Polythymine Nucleotides,dA dT, Poly,dA-dT, Poly,dT, Poly dA
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003593	Cytoplasm	The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)	Protoplasm,Cytoplasms,Protoplasms
D003851	Deoxyribonucleases	Enzymes which catalyze the hydrolases of ester bonds within DNA. EC 3.1.-.	DNAase,DNase,Deoxyribonuclease,Desoxyribonuclease,Desoxyribonucleases,Nucleases, DNA,Acid DNase,Alkaline DNase,DNA Nucleases,DNase, Acid,DNase, Alkaline