Distribution of anticancer antibiotic daunomycin in the rat heart and kidney revealed by immunocytochemistry using monoclonal antibodies |
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Authors: | Kunio Fujiwara Masashi Shin David M Hougaard Lars-Inge Larsson |
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Institution: | (1) Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, Ikeda, 4-22-1, Kumamoto 860-0082, Japan;(2) Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark;(3) Division of Cell Biology, Department of Anatomy and Physiology, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark |
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Abstract: | Two monoclonal antibodies (ADM-1-11 and 79-31 mAbs) were raised against daunomycin (DM) conjugated to bovine serum albumin
via the cross-linker N-(gamma-maleimidobutyryloxy)succinimide. The monoclonal antibodies (mAbs) specifically detected DM as well as its analogs
doxorubicin and epirubicin, but did not react with other anticancer antibiotics, including pepleomycin, mitomycin C, and actinomycin
D. The mAbs reacted strongly with glutaraldehyde-conjugated DM in an enzyme linked immunosorbent assay (ELISA) used as a model
system for immunocytochemistry as well as in appropriately pretreated sections of tissues from animals injected with DM. No
staining occurred in tissues from uninjected animals. In order to perform DM ICC a number of tissue treatment conditions critical
to the detection of low molecular weight substances were employed. Uptake of DM was studied in rats after a single i.v. or
i.p. administration of the drug. In the heart, accumulation of DM occurred in nuclei and in the cytoplasm. In the kidney,
DM immunoreactivity accumulated in all segments of the nephron except for the proximal tubules. Since the proximal tubules
are known to be where a variety of transport systems including P-glycoprotein (Pgp) and organic anion-transporting polypeptides
(OATPs) in drug interactions occur, the absence of DM accumulation in these segments may reflect a transport phenomenon depending
upon such transporters. The availability of methods to study sites of accumulation of DM offers possibilities for understanding
toxic side effects of this drug on the heart and kidney. Moreover, the immunocytochemical methodology developed may prove
useful for the localization of other low molecular weight drugs that can be fixed in situ by glutaraldehyde. |
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Keywords: | Daunomycin Immunocytochemistry Monoclonal antibody Distribution Kidney Heart P-glycoprotein Rat |
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