Immunocytochemical studies on the distribution pattern of daunomycin in rat gastrointestinal tract.
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.
Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, Ikeda 4-22-1, Kumamoto, 860-0082, Japan.
Koji
K
Ohara
Masashi
M
Shin
Hiromichi
H
Nakamuta
Lars-Inge
LI
Larsson
David M
DM
Hougaard
Kunio
K
Fujiwara
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003630:Daunorubicin / Q000032:analysis / Q000493:pharmacokinetics*; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000648:ultrastructure; D007150:Immunohistochemistry; D051381:Rats; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D003630:Daunorubicin