Subcellular distribution of adriamycin in the liver and tumor of 3LL-bearing mice.
The apparent subcellular distribution of adriamycin (ADM) was investigated in the liver and primary or metastatic tumor tissue of C57BL/6 mice bearing i.m. 3LL. ADM was measured by a fluorimetric assay in the various cell components, nuclei (N), mitochondria (MT), microsomes (M) and soluble fraction of cytoplasm (SF), either in vitro at various times of incubation or in vivo after drug injection. In both experimental conditions more than 50% of ADM accumulated in nuclei, whereas only a proportionally low amount of drug has recovered in the other fractions. However, a progressive increase in the percentage of drug stored in M and particularly in MT was noted in vivo in both liver and tumor, reaching in MT 3 times the starting amount on a percentage basis 24 hr after drug treatment. The elimination half-life of ADM was consistently longer in MT and M than in nuclei and total liver, suggesting that M and particularly MT have a higher capacity than nuclei to retain the drug. Work is in progress to evaluate whether this higher ADM accumulation at these subcellular sites is related to higher specific affinity or more persistent binding, like covalent binding to macromolecules, possibly accounting for the mitochondrial injury usually observed after treatment with ADM.
D000818:Animals; D004317:Doxorubicin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D004317:Doxorubicin