title: Immunohistochemical and ultrastructural studies of 2,6-dimethylaniline-induced nasal proliferative lesions in a rat two-stage nasal carcinogenesis model initiated with N-bis(2-hydroxypropyl)nitrosamine.
abstract: Proliferative lesions induced by 2,6-dimethylaniline (DMA) in a two-stage rat nasal carcinogenesis model were immunohistochemically and ultrastructurally investigated. Male F344 rats received diet containing 3,000 ppm DMA for 52 weeks after initiation with a single subcutaneous injection of 2400 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN). Histopathologically, proliferation of Bowman's glands, glandular hyperplasias, dysplastic foci, adenomas, and carcinomas were observed in treated rats. These nasal lesions mostly arose in the olfactory mucosa of the nasal cavity. Immunohistochemically, they were positive for cytokeratin and/or collagen type IV antibodies. Ultrastructurally, intracytoplasmic dense secretory granules (200-850 nm in diameter), identical to those in normal Bowman's glands, were observed in all the lesions, providing further support from an origin from these glands. Based on their cellular characterization, growth pattern and/or proliferative activity, two morphological continua were evident, one from dysplastic foci to carcinomas and the other from proliferation of Bowman's glands to glandular hyperplasias and adenomas. These results suggest that dysplastic foci arise from Bowman's glands and progress to carcinomas, while proliferation of Bowman's glands result in glandular hyperplasias and adenomas.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koujitani
authors.forename: K
authors.initials: K
authors.lastname: Yasuhara
authors.forename: K
authors.initials: K
authors.lastname: Toyosawa
authors.forename: A
authors.initials: A
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Onodera
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Hirose
authors.forename: K
authors.initials: K
authors.lastname: Mitsumori
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000737:chemistry / Q000648:ultrastructure*; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000737:chemistry / Q000648:ultrastructure*; D024141:Collagen Type IV / Q000032:analysis; D003896:Desmosomes / Q000648:ultrastructure; D004032:Diet; D004195:Disease Models, Animal; D004338:Drug Combinations; D007124:Immunoenzyme Techniques; D007279:Injections, Subcutaneous; D007381:Intermediate Filament Proteins / Q000032:analysis; D008297:Male; D009602:Nitrosamines / Q000008:administration & dosage / Q000633:toxicity*; D009669:Nose Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000648:ultrastructure*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000648:ultrastructure*; D051381:Rats; D011916:Rats, Inbred F344; D022142:Secretory Vesicles / Q000648:ultrastructure
chemical_list: D000814:Aniline Compounds; D002273:Carcinogens; D024141:Collagen Type IV; D004338:Drug Combinations; D007381:Intermediate Filament Proteins; D009602:Nitrosamines; C007766:2,6-xylidine; C012457:diisopropanolnitrosamine