Myocardial injury induced by a single dose of adriamycin: an electron microscopic study.
Adriamycin cardiomyopathy has been studied under the electron microscope using myocardial ventircular cells of CRF mice, previously treated with 10 mg/kg body weight of the drug given in a single intravenous injection. Within 10 min myocardial cell nucleoli show a nucleolonema fragmentation, and during the following 3 hours they acquire the nucleolar segregation pattern. Fourteen hours after drug injection, nucleolar morphology again becomes normal, while areas of focal degeneration, characterized by damaged mitochondria and enlarged smooth reticulum cisternae, appear in the sarcoplasm. One to 3 days later the degeneration process involves the myofibrillar component, and after 50 days the great majority of myocardial ventricular cells is damaged. The early appearance and the functional significance of nucleolar segregation support the hypothesis that adriamycin cardiotoxicity might be dependent on its ability to bind to myocardial cell DNA. The consequent failure of RNA and protein synthesis, impairing the continuous renewal of myofibrillar and mitochondrial components of the cell, might explain the progressive myocardial damage.
D000818:Animals; D002466:Cell Nucleolus / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000009:adverse effects* / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D006352:Heart Ventricles / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D009210:Myofibrils / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D012261:Ribonucleoproteins / Q000096:biosynthesis; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors
D012261:Ribonucleoproteins; D012313:RNA; D004317:Doxorubicin; D004247:DNA