PREFERENTIAL OXIDATION OF CARDIAC MITOCHONDRIAL-DNA FOLLOWING ACUTE INTOXICATION WITH DOXORUBICIN

The purpose of this investigation was to determine whether acute doxor ubicin intoxication causes a preferential accumulation of 8-hydroxydeo xyguanosine (8OHdG) adducts to mitochondrial DNA (mtDNA) as opposed to nuclear DNA (nDNA), particularly in cardiac tissue. Adult male rats r eceived 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 g reater increase in 8OHdG adducts to mtDNA compared to nDNA, the concen tration of adducts to both nDNA and mtDNA being 20%-40% greater for he art as opposed to liver. For both tissues, the relative abundance of a dducts was highest at the earliest time-point examined (24 h) and decr eased to control values by 2 weeks. The temporal dilution of 8OHdG add ucts was not the result of cell hyperplasia and was only partially due to amplification of the mitochondrial genome, most probably via an in crease in DNA copy number rather than a stimulation of mitochondrial b iogenesis. (C) 1997 Elsevier Science B.V.