Mechanisms and selectivity of anthracycline aminoglycosides and other intercalating agents.
Many of the antiproliferative actions of daunorubicin and adriamycin are attributable to the results of their interaction with DNA: single and double strand breaks and inhibition of repair and of nucleic acid synthesis. Like other DNA-reactive agents, high cumulative doses produce pharmacological actions and species-specific cytotoxicities in non-proliferating myocardium and nerve cells. Evidence is reviewed suggesting that many, if not all, intercalating agents are membrane-reactive. Thus it seems likely that the selective nature of the responses by various cells and the discrete expressions of cytotoxicity may be determined by binding to specific receptors in membranes of target cells in susceptible organs and species.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA; D004260:DNA Repair / Q000187:drug effects; D004277:DNA, Single-Stranded; D003630:Daunorubicin / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects; D004579:Electron Transport / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009417:Nerve Tissue / Q000187:drug effects; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects
D004277:DNA, Single-Stranded; D011955:Receptors, Drug; D004317:Doxorubicin; D004247:DNA; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D003630:Daunorubicin