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- Title
Induction of squamous cell carcinoma of forestomach in diabetic rats by single alloxan treatment.
- Authors
Kodama, Yasushi; Ozaki, Kiyokazu; Sano, Tomoya; Matsuura, Tetsuro; Akagi, Hiroyuki; Narama, Isao
- Abstract
Male rats of WBN/Kob strain are one of the diabetic model animals and develop long-lasting diabetic symptoms and some complications from about 40 weeks of age without any treatment. A single intravenous dose of alloxan, a non-genotoxic diabetogenic chemical, frequently induced proliferative lesions of squamous epithelium in tongue, esophagus and forestomach of male and female WBN/Kob rats, and hastened the onset and acceleration of diabetic conditions. Histopathologically, proliferative changes of squamous cell of forestomach varied with the severity of hyperplasia in alloxan-treated rats (100% of 31 males and 94.1% of 17 females) and progressed to SCC in approximately 20% of all rats. Metastasis to regional lymph nodes was also observed in two cases. Proliferative changes were most severe in the forestomach and were constantly accompanied with chronic suppurative inflammation of the mucosal epithelium with infection of filamentous fungi and/or bacterial colonies. In contrast, forestomach of the spontaneously diabetic male rats showed only slight hyperplasia of the mucosal epithelium confined to the limiting ridge in approximately 30% of the cases. All non-diabetic female rats showed neither proliferative changes nor the inflammatory process in the mucosa. Immunohistochemically, COX-2 and iNOS were positive in these chronic suppurative inflammatory lesions accompanied by proliferative squamous epithelium. From these results, it is suggested that chronic inflammatory processes play an important role in the pathogenesis of alloxan-induced SCC. An experimental system of alloxan-induced SCC might serve as a suitable model for the study of the inflammation-related promotion of carcinogenesis. ( Cancer Sci 2006; 97: 1023–1030)
- Subjects
RATS; ANIMAL models in research; TREATMENT of diabetes; HISTOPATHOLOGY; SQUAMOUS cell carcinoma; METASTASIS
- Publication
Cancer Science, 2006, Vol 97, Issue 10, p1023
- ISSN
1347-9032
- Publication type
Article
- DOI
10.1111/j.1349-7006.2006.00279.x