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Titolo:
Cardioselective and cumulative oxidation of mitochondrial DNA following subchronic doxorubicin administration
Autore:
Serrano, J; Palmeira, CM; Kuehl, DW; Wallace, KB;
Indirizzi:
Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA Univ Minnesota Duluth MN USA 55812 ochem & Mol Biol, Duluth, MN 55812 USA US EPA, Midcontinent Ecol Div, NHEERL, Duluth, MN 55804 USA US EPA DuluthMN USA 55804 ntinent Ecol Div, NHEERL, Duluth, MN 55804 USA Univ Coimbra, Dept Zool, Ctr Neurosci, P-3000 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3000 Neurosci, P-3000 Coimbra, Portugal
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
fascicolo: 1, volume: 1411, anno: 1999,
pagine: 201 - 205
SICI:
0005-2728(19990421)1411:1<201:CACOOM>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; NUCLEAR-DNA; DAMAGE; REPAIR; ADRIAMYCIN; 8-HYDROXYDEOXYGUANOSINE; MUTATIONS; ACCUMULATION; BINDING; CANCER;
Keywords:
adriamycin; doxorubicin; mitochondrial DNA; 8-hydroxydeoxyguanosine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Wallace, KB Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA Univ Minnesota Duluth MN USA 55812 Biol, Duluth, MN 55812 USA
Citazione:
J. Serrano et al., "Cardioselective and cumulative oxidation of mitochondrial DNA following subchronic doxorubicin administration", BBA-BIOENER, 1411(1), 1999, pp. 201-205

Abstract

We recently reported the preferential accumulation of 8-hydroxydeoxyguanosine (8OHdG) adducts in cardiac mitochondrial DNA (mtDNA) following acute intoxication of rats with doxorubicin (C.M. Palmeira et al., Biochim. Biophys. Acta, 1321 (1997) 101-106). The concentration of 8OHdG adducts decreased to control values within 2 weeks. Since conventional antineoplastic therapyentails repeated administration of small doses of doxorubicin, it was of interest to characterize the kinetics for the accumulation and repair of 8OHdG adducts in the various DNA fractions. Weekly injections of doxorubicin (2 mg/kg, i.p.) to adult male Sprague-Dawley rats caused a cumulative dose-dependent increase in the concentration of 8OHdG adducts in both mtDNA and nuclear DNA (nDNA) from heart and liver. Following six weekly injections, the concentration of 8OHdG in cardiac mtDNA was 50% higher than liver mtDNA and twice that of cardiac nDNA, In contrast to the rapid repair of 8OHdG observed during the first days following an acute intoxicating dose of doxorubicin, the concentration of 8OHdG 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 8OHdG adducts tomtDNB is consistent with the implication of mitochondrial dysfunction in the cumulative and irreversible cardiotoxicity observed clinically in patients receiving doxorubicin cancer chemotherapy. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 06:23:23