title: N-methyl-N-nitrosourea-induced schwannomas in male Sprague-Dawley rats with a literature review of inducible and spontaneous lesions.
abstract: N-methyl-N-nitrosourea (MNU) possesses peripheral nervous system carcinogenic activity in rats and induces benign and malignant schwannomas in systemic organs. In this retrospective study, we compared the characteristics of various immunohistochemical markers in MNU-induced schwannomas in male Crj:CD(SD)IGS rats including: vimentin (Vim), S100, p75 nerve growth factor receptor (LNGFR), CD57, pancytokeratin (CK), myoglobin, desmin and α smooth muscle actin (SMA). Single intraperitoneal exposures of 50 or 75mg/kg MNU in male rats at the age of 4 weeks induced schwannomas in 43 surviving and terminated rats up to 30-weeks-old. The incidence rate of neoplastic lesions was 37% (16 of 43 rats). Benign schwannomas (mesentery, pancreas, thymus) and malignant schwannomas (subendocardium, cardiac intramural, thoracic cavity, abdominal cavity, prostate), occurred in nine and seven rats, respectively. All neoplastic lesions were moderately or strongly positive for Vim, S100 and LNGFR proteins. Benign tumors were weakly positive and malignant tumors strongly positive for Ki-67, suggesting a high active proliferation rate of Schwann cell precursors. All lesions were negative for CD57, CK, myoglobin, desmin and SMA. This data may provide useful immunohistochemical information for the investigation of schwannomas in rat chemical carcinogenicity studies.
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan. Electronic address: yoshizak@hirakata.kmu.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Yuki
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; Division of Diagnostic Cytopathology and Histopathology, Kansai Medical University Medical Center, Fumizono 10-15, Moriguchi, Osaka 570-8507, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Emoto
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.affiliation: Cellular & Molecular Pathology Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Elmore
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D016208:Databases, Factual; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009442:Neurilemmoma / Q000139:chemically induced* / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: D002273:Carcinogens; D008770:Methylnitrosourea
keywords: Immunohistochemistry; N-methyl-N-nitrosourea; Neurofibromatosis; Ntp; Rat; Schwannoma