Open AccessNovel medium‐term carcinogenesis model for lung squamous cell carcinoma induced by N ‐nitroso‐tris‐chloroethylurea in mice
Author(s) -
Tago Yoshiyuki,
Yamano Shotaro,
Wei Min,
Kakehashi Anna,
Kitano Mitsuaki,
Fujioka Masaki,
Ishii Naomi,
Wanibuchi Hideki
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12289
Subject(s) - pathology , adenocarcinoma , carcinogenesis , lung cancer , lung , squamous cell carcinoma of the lung , dysplasia , carcinoma , large cell , cytokeratin , medicine , immunohistochemistry , squamous carcinoma , cancer research , cancer
Targeted treatments for lung cancer based on pathological diagnoses are required to enhance therapeutic efficacy. There are few well‐established animal models for lung squamous cell carcinoma although several highly reproducible mouse models for lung adenoma and adenocarcinoma are available. This study was carried out to establish a new lung squamous cell carcinoma mouse model. In the first experiment, female A / J mice were painted topically on back skin twice weekly with 75 μL 0.013 M N‐nitroso‐tris‐chloroethylurea for 2, 4, and 8 weeks ( n = 15–20 per group) as initiation of lung lesions, and surviving mice were killed at 18 weeks. In the second experiment, mice were treated as above for 4 weeks and killed at 6, 12, or 18 weeks ( n = 3 per group). Lung lobes were subjected to histopathological, immunohistochemical, immunoblotting, and ultrastructural analyses. In the case of treatment for 2, 4, and 8 weeks, incidences of lung squamous cell carcinoma were 25, 54, and 71%, respectively. Cytokeratin 5/6 and epidermal growth factor receptor were clearly expressed in dysplasia and squamous cell carcinoma. Desmosomes and tonofilaments developed in the squamous cell carcinoma. Considering the carcinogenesis model, we conclude that 2 or 4 weeks of N ‐nitroso‐tris‐chloroethylurea treatment may be suitable for investigating new chemicals for promotional or suppressive effects on lung squamous cell carcinoma.