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, Gurmukh Singh, S. L. Katyal

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Abstract

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-μl 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.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalAmerican Journal of Pathology
Volume139
Issue number2
StatePublished - Jan 1 1991
Externally publishedYes

Fingerprint

Urea
Carcinogenesis
Neoplasms
Metaplasia
Keratins
Hyperplasia
Clara cell antigen
Adenosquamous Carcinoma
Alveolar Epithelial Cells
Bronchioles
Chromogranin A
Bombesin
Neuroendocrine Cells
Apoproteins
Avidin
Phosphopyruvate Hydratase
Biotin
Acetone
Surface-Active Agents
Paraffin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Mouse bronchiolar cell carcinogenesis : Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2-chloroethyl) ureas. / Rehm, S.; Lijinsky, W.; Singh, Gurmukh; Katyal, S. L.

In: American Journal of Pathology, Vol. 139, No. 2, 01.01.1991, p. 413-422.

Research output: Contribution to journalArticle

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