title: Cutaneous Epithelial Lesions Induced by N-Methyl-N-nitrosourea in Male Sprague-Dawley Rats: A Possible Animal Model for Human Keratoacanthoma.
abstract: A single intraperitoneal injection of 50 or 75 mg/kg N-methyl-N-nitrosourea in male Sprague-Dawley rats at 4 weeks of age, dose-dependently resulted in cutaneous epithelial cysts and tumors of pilosebaceous origin. Cysts were composed of epidermal cysts or mixed epidermal and inner root sheath hybrid cysts. The majority of induced tumors were keratoacanthomas. A few tumors were trichofolliculomas, trichoblastomas, pilomatricomas, or sebaceous adenomas. All tumors were benign pilosebaceous tumors. Keratoacanthomas were crater-shaped tumors with thick infoldings of epithelium containing keratohyalin granules (epidermal lip) that abruptly changed to epithelium containing trichohyalin granules. The morphological similarity and resemblance of keratin 1, 10, and 14 profiles, and p63 and β-catenin expression between mixed epidermal and inner root sheath hybrid cysts and keratoacanthomas suggests that hybrid cysts progressed to keratoacanthomas, and the cells from infundibular cells to inner root sheath cells of the pilar segment seem to be the origin of rat keratoacanthomas. Immunohistochemical localization of keratins 1, 10 and 14, p63, and β-catenin in trichofolliculoma, trichoblastoma, and pilomatricoma, as well as keratoacanthoma, may indicate tumor histogenesis.
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan yukimic@hirakata.kmu.ac.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Yuki
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Emoto
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Department of Pathology II, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
authors.affiliation: Department of Dermatology, Meiwa Hospital, Nishinomiya, Hyogo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurokawa
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D004195:Disease Models, Animal; D004814:Epidermal Cyst / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007636:Keratoacanthoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008770:Methylnitrosourea; D009375:Neoplasms, Glandular and Epithelial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D008770:Methylnitrosourea
keywords: Epidermal cyst; MNU; hybrid cyst; keratoacanthoma; pilomatricoma; rat; sebaceous adenoma; trichoblastoma; trichofolliculoma