You are here:
CARDIOSELECTIVE AND CUMULATIVE OXIDATION OF MITOCHONDRIAL DNA FOLLOWING SUBCHRONIC DOXORUBICIN ADMINISTRATION
Citation:
Serrano, J A., C. M. Palmeira, D W. Kuehl, AND K. B. Wallace. CARDIOSELECTIVE AND CUMULATIVE OXIDATION OF MITOCHONDRIAL DNA FOLLOWING SUBCHRONIC DOXORUBICIN ADMINISTRATION. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 1411:201-205, (1999).
Description:
We recently reported the preferential accumulation of 8-hydroxydeoxyguanosine (80HdG) adducts in cardiac mitrochondrial DNA (mDNA) following acute intoxication of rats with doxorubicin. The concentration of 80HdG adducts decreased to control values within 2 weeks. Since conventional antineoplastic therapy entails repeated administration of small doses of doxorubicin, it was of interest to characterize the kinetics for the accumulation and repair of 80HdG adducts in the various DNA fractions. Weekly injections of doxorubicin to adult male Sprague-Dawley rats caused a cumulative dose-dependent increase in the concentration of 80HdG adducts in both mtDNA and nuclear DNA from heart to liver. Following six weekly injections, the concentration of 80HdG adducts remained constant between 1 and 5 weeks following the last injection. This was true for all DNA fractions examined. The cardioselective accumulation and persistence of SOHdG adducts to mtDNA is consistent with the implication of mitochondrial dysfunction in the cumulative and irreversible cardiotoxicity observed clinically in patients receiving doxorubicin cancer chemotherapy.