Immunocytochemical studies on the distribution pattern of daunomycin in rat gastrointestinal tract |
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Authors: | Koji Ohara Masashi Shin Hiromichi Nakamuta Lars-Inge Larsson David M Hougaard Kunio Fujiwara |
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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) Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, Hirokoshingai 5-1-1, Kure, Hiroshima 737-0112, Japan;(3) Department of Clinical Biochemistry, Statens Serum Institute, Copenhagen, Denmark;(4) Department of Cell Biology IBHV, Faculty of Life Sciences, University of Copenhagen, Gronnegaardsvej 7, 1870 Frederiksberg C, Denmark |
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Abstract: | The cancer drug daunomycin is used in treatment of leukemia but possesses severe side effects that involve the gastrointestinal
tract. We therefore used a newly developed immunocytochemical procedure to determine the distribution of DM in the gastrointestinal
tracts of rats after i.v. injection. Two hours after injection, DM was diffusely distributed in nuclei and most parts of the
cytoplasm of intestinal epithelial cells. The cytoplasmic immunoreactivity for DM was most pronounced in small granules of
the apical cytoplasm. Sixteen hours after injection, DM immunostaining was by and large absent in the villous epithelium but
persisted in the intestinal crypts. In addition, staining was also detected in endothelial cells, scattered cells of the lamina
propria and in smooth muscle cells. After 5 days, only little staining for DM remained. Similar findings were made in the
colon. In the gastric mucosa, DM accumulation persisted at 16 h in some glandular cells but was lost from the surface epithelium.
No staining was detected in saline-injected control rats. The distribution of DM accumulation correlated partially with the
distribution of apoptotic cells as detected by the TUNEL procedure. Our results pinpoint that DM may exert prolonged effects
on glandular and regenerative cells of the gastrointestinal tract—an observation that may explain the gastrointestinal toxicity
of the drug. It seems possible that DM accumulation in surface epithelial cells is rapidly cleared through drug transporters. |
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Keywords: | Daunomycin Immunocytochemistry Monoclonal antibody Rat Distribution Gastrointestinal tract Apoptosis |
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