title: Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats.
abstract: We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37-45 weeks after the treatment with STZ (50 or 75mg/kg, i.v.) and NA (350mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan; Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Rinkuu Ourai Kita 1-58, Izumisano, Osaka 598-8531, Japan. Electronic address: yuuki.katou@shionogi.co.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuno
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Fujisawa
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Mikinori
authors.initials: M
authors.lastname: Torii
authors.affiliation: Drug Safety Evaluation, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hishikawa
authors.affiliation: Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Rinkuu Ourai Kita 1-58, Izumisano, Osaka 598-8531, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Rinkuu Ourai Kita 1-58, Izumisano, Osaka 598-8531, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Rinkuu Ourai Kita 1-58, Izumisano, Osaka 598-8531, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D007516:Adenoma, Islet Cell; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D004195:Disease Models, Animal; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D018358:Neuroendocrine Tumors / Q000139:chemically induced* / Q000473:pathology*; D009536:Niacinamide / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D014803:Vitamin B Complex / Q000633:toxicity
chemical_list: D000903:Antibiotics, Antineoplastic; D014803:Vitamin B Complex; D009536:Niacinamide; D013311:Streptozocin
keywords: Adrenal; Diabetes; Glucose; Insulin; Kidney; Liver