Effect of adriamycin on heart mitochondrial DNA.
The effect of Adriamycin on rat heart mitochondrial DNA was determined by initially labelling the DNA with [Me-14C]thymidine. Animals subsequently received intravenously either Adriamycin (10 mg/kg) or saline (1 ml/kg) (control group). Animals later received [Me-3H]thymidine and were killed at 6, 14, 24 and 36 h after this. The heart mitochondrial DNA was separated into the linear, non-supercoiled and supercoiled forms by ultracentrifugation on formamide/sucrose sedimentation gradients, and the amount of 14C and 3H incorporated into the various forms of the DNA was determined by scintillation counting. The data suggest that Adriamycin may cause breakage of the mitochondrial DNA helix, and that it slows the rate of mitochondrial DNA synthesis and the formation of complete DNA molecules. These experiments show that Adriamycin does interact with heart mitochondrial DNA, and may explain the cardiac dysfunction association with Adriamycin use.
Ellis
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Baptist Medical Center-Princeton, Medical Education Department, Birmingham, AL 35211.
Ellis
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Blakemore
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D000818:Animals; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D004317:Doxorubicin; D004247:DNA; D013936:Thymidine