Rapid apoptotic changes in the gastric glandular epithelium of rats administered intraperitoneally with fusarenon-X.
Fusarenon-X (FX) 1.5 mg/kg was administered intraperitoneally (i.p.) to 6-week-old male Wistar rats for examination of pathologic effects on the glandular stomach. Rats ip-treated with sterilized physiological saline were used as control. FX-administered rats showed dilatation of the stomach with increased fluid contents after 1-4 hr. Light microscopically, a few apoptotic karyopyknosis were seen in chief cells in the basal region at 1 hr postadministration (PA) and mitotic inhibition was evident after 2 hr PA. Marked apoptosis of nuclear pyknosis and cytoplasmic inclusions in both zymogenic and oxyntic cells developed from basal to middle regions of the gastric mucous membrane at 2-4 hr PA with a peak at 3 hr. Apoptotic changes of differentiating neck cells and surface epithelia were less evident. Electron microscopy revealed that the chief cells were the main target of FX-induced apoptotosis. The parietal cells were secondarily involved because they phagocytosed chief cell-derived apoptotic bodies. In situ detection of DNA breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction revealed the positive nuclei after 1 hr PA, which increased with time and reached a peak at 3 hr PA, in accordance with apoptotic changes in histological study. Agarose gel electrophoresis of DNA isolated from the gastric mucosae of FX-administered rats showed ladder pattern of DNA fragments after 1.5 hr PA with the maximum distinctness at 3 hr PA.
Li
J
J
Laboratory of Veterinary Pathology, Faculty of Agriculture, Kagoshima University, Japan.
Shimizu
T
T
Miyoshi
N
N
Yasuda
N
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D004247:DNA / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D002479:Inclusion Bodies / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
D009183:Mycotoxins; D014255:Trichothecenes; C002469:fusarenon-X; D004247:DNA