The fidelity of mouse liver mitochondrial DNA polymerase following long-term administration of carbon tetrachloride, diethylnitrosamine, or phenobarbital.

The fidelity of liver mtDNA polymerase was compared in control mice, in mice treated chronically with diethylnitrosamine (DEN), carbon tetrachloride (CCl4), or phenobarbital sodium (PBNa). Liver mitochondria were isolated, and the mtDNA polymerase activity was obtained by high-salt extraction and subjected to chromatography first on DEAE-cellulose (DE 52) and then on heparin-Sepharose. Fidelity of the mtDNA polymerase was determined, after heparin-Sepharose chromatography, by measuring the relative incorporation of a complementary nucleotide, [32P]dTMP, and a noncomplementary nucleotide, [3H]dGMP, into acid-precipitable material with enzyme activity directed by the template-primer poly(A) . oligo(dT) 12-18. A decrease in fidelity (increase in relative incorporation [3H]dGMP) was observed after 12 or 13 weeks of treatment with DEN. The fidelity of mouse liver mtDNA polymerase also was decreased after 12 weeks of treatment with PBNa. By contrast, treatment for 12 weeks with CCl4 was accompanied either by increased fidelity (decrease in the relative incorporation of [3H]dGMP) or no change in fidelity.