J.C. Blanchard , Y.-J. Schneider , R. Baurain, A. Trouet
{"title":"柔红霉素、阿霉素及其dna复合物在大鼠心室的积累、代谢和亚细胞定位","authors":"J.C. Blanchard , Y.-J. Schneider , R. Baurain, A. Trouet","doi":"10.1016/0014-2964(81)90121-3","DOIUrl":null,"url":null,"abstract":"<div><p>The accumulation in rat heart ventricles, the presence of metabolites and the subcellular localization of daunorubicin (DNR), doxorubicin (DOX) and their DNA complexes were investigated. After intravenous perfusion of free DNR or DOX, equal amounts of the drugs are recovered in the heart, whereas after injection of their DNA complexes, the accumulation levels represent <em>42%</em> (DNR) and <em>32%</em> (DOX) of those reached with the free drugs. Daunorubicinol and daunomycinone are detected after administration of DNR or DNR-DNA but only trace amounts of metabolites are found with DOX and DOX-DNA. Subcellular distributions of DNR injected as free or DNA complex are similar. Isopycnic and differential centrifugations indicate that DNR could be associated with nuclear DNA and to a smaller extent with lysosomes. By contrast, after injection of free or complexed DOX the drug is almost exclusively associated with the nuclear DNA. The mechanisms by which these drugs are accumulated by the heart and the relation with their cardiotoxicities are discussed.</p></div>","PeriodicalId":100497,"journal":{"name":"European Journal of Cancer (1965)","volume":"17 3","pages":"Pages 297-305"},"PeriodicalIF":0.0000,"publicationDate":"1981-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0014-2964(81)90121-3","citationCount":"15","resultStr":"{\"title\":\"Accumulation, metabolism and subcellular localization of daunorubicin, doxorubicin and their DNA-complexes in rat heart ventricles\",\"authors\":\"J.C. Blanchard , Y.-J. Schneider , R. Baurain, A. Trouet\",\"doi\":\"10.1016/0014-2964(81)90121-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The accumulation in rat heart ventricles, the presence of metabolites and the subcellular localization of daunorubicin (DNR), doxorubicin (DOX) and their DNA complexes were investigated. After intravenous perfusion of free DNR or DOX, equal amounts of the drugs are recovered in the heart, whereas after injection of their DNA complexes, the accumulation levels represent <em>42%</em> (DNR) and <em>32%</em> (DOX) of those reached with the free drugs. Daunorubicinol and daunomycinone are detected after administration of DNR or DNR-DNA but only trace amounts of metabolites are found with DOX and DOX-DNA. Subcellular distributions of DNR injected as free or DNA complex are similar. Isopycnic and differential centrifugations indicate that DNR could be associated with nuclear DNA and to a smaller extent with lysosomes. By contrast, after injection of free or complexed DOX the drug is almost exclusively associated with the nuclear DNA. The mechanisms by which these drugs are accumulated by the heart and the relation with their cardiotoxicities are discussed.</p></div>\",\"PeriodicalId\":100497,\"journal\":{\"name\":\"European Journal of Cancer (1965)\",\"volume\":\"17 3\",\"pages\":\"Pages 297-305\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1981-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/0014-2964(81)90121-3\",\"citationCount\":\"15\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer (1965)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/0014296481901213\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer (1965)","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/0014296481901213","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Accumulation, metabolism and subcellular localization of daunorubicin, doxorubicin and their DNA-complexes in rat heart ventricles
The accumulation in rat heart ventricles, the presence of metabolites and the subcellular localization of daunorubicin (DNR), doxorubicin (DOX) and their DNA complexes were investigated. After intravenous perfusion of free DNR or DOX, equal amounts of the drugs are recovered in the heart, whereas after injection of their DNA complexes, the accumulation levels represent 42% (DNR) and 32% (DOX) of those reached with the free drugs. Daunorubicinol and daunomycinone are detected after administration of DNR or DNR-DNA but only trace amounts of metabolites are found with DOX and DOX-DNA. Subcellular distributions of DNR injected as free or DNA complex are similar. Isopycnic and differential centrifugations indicate that DNR could be associated with nuclear DNA and to a smaller extent with lysosomes. By contrast, after injection of free or complexed DOX the drug is almost exclusively associated with the nuclear DNA. The mechanisms by which these drugs are accumulated by the heart and the relation with their cardiotoxicities are discussed.