Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin

C. M. Palmeira; J. Serrano; D. W. Kuehl; Kendall B Wallace

doi:10.1016/S0005-2728(97)00055-8

Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin

C. M. Palmeira, J. Serrano, D. W. Kuehl, Kendall B Wallace

Biomedical Sciences

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95 Scopus citations

Abstract

The purpose of this investigation was to determine whether acute doxorubicin intoxication causes a preferential accumulation of 8-hydroxydeoxyguanosine (8OHdG) adducts to mitochondrial DNA (mtDNA) as opposed to nuclear DNA (nDNA), particularly in cardiac tissue. Adult male rats received a single i.p. bolus of doxorubicin (15 mg/kg) and were killed 1-14 days later. Acute intoxication with doxorubicin caused a 2-fold greater increase in 8OHdG adducts to mtDNA compared to nDNA, the concentration of adducts to both nDNA and mtDNA being 20%-40% greater for heart as opposed to liver. For both tissues, the relative abundance of adducts was highest at the earliest time-point examined (24 h) and decreased to control values by 2 weeks. The temporal dilution of 8OHdG adducts was not the result of cell hyperplasia and was only partially due to amplification of the mitochondrial genome, most probably via an increase in DNA copy number rather than a stimulation of mitochondrial biogenesis.

Original language	English (US)
Pages (from-to)	101-106
Number of pages	6
Journal	Biochimica et Biophysica Acta - Bioenergetics
Volume	1321
Issue number	2
DOIs	https://doi.org/10.1016/S0005-2728(97)00055-8
State	Published - Aug 22 1997

Bibliographical note

Funding Information:
This work was supported in part by Kalsec. The manuscript was not subjected to internal Agency review and, thus, the opinions are those of the authors and are not officially endorsed by the U.S. Environmental Protection Agency. Mention of trade names or commercial products does not constitute endorsement nor is it intended to imply any form of judgment by the authors. CMP is the recipient of a Fellowship from the Portuguese JNICT (PRAXIS XXI/BPD/4239/94).

Keywords

8-Hydroxydeoxyguanosine
Adriamycin
Doxorubicin
Mitochondrion

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abstract = "The purpose of this investigation was to determine whether acute doxorubicin intoxication causes a preferential accumulation of 8-hydroxydeoxyguanosine (8OHdG) adducts to mitochondrial DNA (mtDNA) as opposed to nuclear DNA (nDNA), particularly in cardiac tissue. Adult male rats received a single i.p. bolus of doxorubicin (15 mg/kg) and were killed 1-14 days later. Acute intoxication with doxorubicin caused a 2-fold greater increase in 8OHdG adducts to mtDNA compared to nDNA, the concentration of adducts to both nDNA and mtDNA being 20%-40% greater for heart as opposed to liver. For both tissues, the relative abundance of adducts was highest at the earliest time-point examined (24 h) and decreased to control values by 2 weeks. The temporal dilution of 8OHdG adducts was not the result of cell hyperplasia and was only partially due to amplification of the mitochondrial genome, most probably via an increase in DNA copy number rather than a stimulation of mitochondrial biogenesis.",

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N2 - The purpose of this investigation was to determine whether acute doxorubicin intoxication causes a preferential accumulation of 8-hydroxydeoxyguanosine (8OHdG) adducts to mitochondrial DNA (mtDNA) as opposed to nuclear DNA (nDNA), particularly in cardiac tissue. Adult male rats received a single i.p. bolus of doxorubicin (15 mg/kg) and were killed 1-14 days later. Acute intoxication with doxorubicin caused a 2-fold greater increase in 8OHdG adducts to mtDNA compared to nDNA, the concentration of adducts to both nDNA and mtDNA being 20%-40% greater for heart as opposed to liver. For both tissues, the relative abundance of adducts was highest at the earliest time-point examined (24 h) and decreased to control values by 2 weeks. The temporal dilution of 8OHdG adducts was not the result of cell hyperplasia and was only partially due to amplification of the mitochondrial genome, most probably via an increase in DNA copy number rather than a stimulation of mitochondrial biogenesis.

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Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin

Abstract

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