This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rehm, S. Articles by Katyal, S. L. Search for Related Content PubMed PubMed Citation Articles by Rehm, S. Articles by Katyal, S. L.

American Journal of Pathology, Vol 139, 413-422, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Mouse bronchiolar cell carcinogenesis. Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2- chloroethyl) ureas

S Rehm, W Lijinsky, G Singh and SL Katyal
Division of Cancer Etiology, National Cancer Institute, Frederick, Maryland 21702-1201.

Female Swiss mice (Cr:NIH(S)) developed bronchiolar cell hyperplasia, dysplasia, metaplasia, and various morphologic types of bronchiolar cell tumors after topical (skin) application of N-nitroso-methyl-bis- chloroethylurea (NMBCU) or N-nitroso-tris-chloroethylurea (NTCU). These compounds are the first found to induce systemically bronchiolar cell tumors in mice in high incidence. Twice a week, with a 3-day interval, a 25-microliter drop of 0.04 mol/l (molar) NMBCU or NTCU in acetone was applied to the shaved interscapular integument for a maximum of 35 to 40 weeks. The earliest lung neoplasms were seen in mice that died after 23 weeks of treatment and affected 11 of 19 with NMBCU and 14 of 19 with NTCU treatment. Tumor growth pattern was nodular or the neoplastic tissue was frequently disseminated throughout the parenchyma, starting from multicentric peribronchiolar foci. The most common tumor types were squamous cell carcinomas and adenosquamous carcinomas, followed by adenocarcinomas with or without secretory cells, and a single ciliated- cell tumor. Histochemical and immunohistochemical studies were carried out on paraffin-embedded lungs using the avidin-biotin immunoperoxidase complex procedure and antisera against keratin, Clara cell antigen, surfactant apoprotein, neuron-specific enolase, bombesin, and chromogranin A. In several mice from both groups, hyperplasias and tumors were composed of cells expressing Clara cell antigen. No tumor cells were found expressing alveolar type II or neuroendocrine cell markers. It appeared that bronchiolar cells, in particular Clara cells, had migrated from terminal bronchioles or invaded bronchiolar walls to extend into the alveolar parenchyma. Squamous cell metaplasia with keratin expression was seen within airways or associated with glandular tumors, especially at the periphery. A unique cell type, with large eosinophilic globules and associated eosinophilic crystals, was seen lining airways or forming hyperplastic and neoplastic lesions. N- nitroso-methyl-bis-chloroethylurea- and NTCU-induced mouse bronchiolar cell alterations could be an interesting new model to study mechanisms of bronchiolar cell differentiation and tumor formation.

This article has been cited by other articles:

				N. Wakamatsu, T. R. devereux, H.-H. L. Hong, and R. C. Sills Overview of the Molecular Carcinogenesis of Mouse Lung Tumor Models of Human Lung Cancer Toxicol Pathol, January 1, 2007; 35(1): 75 - 80. [Abstract] [Full Text] [PDF]

				R. Meuwissen and A. Berns Mouse models for human lung cancer Genes & Dev., March 15, 2005; 19(6): 643 - 664. [Abstract] [Full Text] [PDF]

				E. S. Fiala, O. S. Sohn, C.-X. Wang, E. Seibert, J. Tsurutani, P. A. Dennis, K. El-Bayoumy, R. S. Sodum, D. Desai, J. Reinhardt, et al. Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E Carcinogenesis, March 1, 2005; 26(3): 605 - 612. [Abstract] [Full Text] [PDF]

				A. Yu. Nikitin, A. Alcaraz, M. R. Anver, R. T. Bronson, R. D. Cardiff, D. Dixon, A. E. Fraire, E. W. Gabrielson, W. T. Gunning, D. C. Haines, et al. Classification of Proliferative Pulmonary Lesions of the Mouse: Recommendations of the Mouse Models of Human Cancers Consortium Cancer Res., April 1, 2004; 64(7): 2307 - 2316. [Abstract] [Full Text] [PDF]

				Y. Wang, Z. Zhang, Y. Yan, W. J. Lemon, M. LaRegina, C. Morrison, R. Lubet, and M. You A Chemically Induced Model for Squamous Cell Carcinoma of the Lung in Mice: Histopathology and Strain Susceptibility Cancer Res., March 1, 2004; 64(5): 1647 - 1654. [Abstract] [Full Text] [PDF]

				R. J. Mason, M. Kalina, L. D. Nielsen, A. M. Malkinson, and J. M. Shannon Surfactant Protein C Expression in Urethane-Induced Murine Pulmonary Tumors Am. J. Pathol., January 1, 2000; 156(1): 175 - 182. [Abstract] [Full Text] [PDF]