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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.241 5年影响因子: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.v27.i4.30
pages 267-276

Immunohistochemical Study of Fibrosis and Adenocarcinoma in Dominant-Negative p53 Transgenic Mice Exposed to Chrysotile Asbestos and Benzo(a)pyrene

Herman T. Yee
Departments of Pathology and Environmental Medicine, and Division of Pulmonary and Critical Care Medicine. NYU School of Medicine, New York, NY 10016
Ting-An Yie
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Judith D. Goldberg
Departments of Pathology and Environmental Medicine, and Division of Pulmonary and Critical Care Medicine. NYU School of Medicine, New York, NY 10016
Kam Meng Tchou Wong
Departments of Pathology and Environmental Medicine, and Division of Pulmonary and Critical Care Medicine. NYU School of Medicine, New York, NY 10016
William N. Rom
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

ABSTRACT

We evaluated the mechanisms using immunohistochemistry whereby chrysotile asbestos and benzo(a)pyrene (BaP) instilled intratracheally into lung-specific dominant-negative p53 (dnp53) mice might interact in causing lung carcinomas and fibrosis. Chrysotile asbestos and benzo(a)pyrene (BaP) were instilled intratracheally into lung-specific dominant-negative p53 (dnp53) and control mice. The mice were sacrificed at 12 months and their lungs examined for lung carcinomas and fibrosis. Immunostains for proteins related to apoptosis, fibrogen-esis, matrix remodeling and inflammation were performed. The dnp53 mice had increased numbers of lung adenocarcinomas with BaP alone and the combination of chrysotile and BaP (the latter was additive but not significant). Several atypical adenomatous hyperplasia lesions were found in the combined treatment group. dnp53 and FVBN control mice developed nodular buds of fibrotic lung tissue after chrysotile asbestos exposure that were localized in respiratory bronchioles; these lesions had significant increases in immunohistochemical staining for TGF-β, MMP-7 and -9, MIG-1, and SDF-1. Fibrotic lesions in mice exposed to chrysotile had increased collagen demonstrated by picrosirius red staining. The dnp53 mice with adenocarcinomas had increased SDF-1, TGF-β, MMP-9 and -7, Cyclin D, and MIG-1 immunostaining in the chrysotile and combined treatment groups. We conclude that BaP and the combination of BaP plus chrysotile asbestos are potent inducers of adenocarcinoma in dnp53 mice and that the inflammatory cytokines and proteases MMP-7 and -9, MIG-1, and SDF-1, and growth factors Cyclin D and TGF-β are increased in the specific lesions.


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