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Clara cell antigen in normal and migratory dysplastic Clara cells, and bronchioloalveolar carcinoma of Syrian hamsters induced by N-nitrosomethyl-n-heptylamine

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Virchows Archiv B

Summary

Histogenetic features of lung tumours were studied in Syrian hamsters that had been induced with 6.8 mgN-nitrosomethyl-n-heptylamine/animal by gavage once a week for 35 weeks. At intervals from experimental week 2 until week 46, pulmonary tissues from hamsters were examined by light and electron microscopy. This report describes early hyperplastic lesions associated with terminal bronchioles and the progression of these lesions to bronchioloalveolar tumours. Using immunohistochemical and ultrastructural colloidal gold labelling techniques, hamster Clara cell antigen was found to be localized in Clara cell granules and smooth endoplasmic reticulum of normal cells, in dysplastic Clara cells migrating through basement membrane defects or from the open end of terminal bronchioles, and in hyperplastic peribronchiolar cell foci. The latter progressed to bronchioloalveolar tumours growing out along alveolar basement membranes in a characteristic lace-like, lepidic pattern. Tumours were composed of secretory (Clara), ciliated, mucous, and undifferentiated cells, as well as trapped, non-neoplastic alveolar type II cells. Hyperplastic neuroendocrine cell foci lining airways were immunoreactive for chromogranin, but these cells did not participate in the pre-neoplastic or neoplastic process. It is suggested that bronchioloalveolar carcinomas in hamsters are derived from bronchiolar secretory (Clara) cells growing along alveolar walls, differentiating into other bronchiolar cell types and entrapping resident alveolar type II cells. Due to the migratory capacity of Clara cells, it is also possible for tumours composed of bronchiolar cells to develop at the lung periphery.

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  1. William Lijinsky

    Present address: , 5521 Woodlyn Rd, 21702, Frederick, MD, USA

Authors and Affiliations

  1. Tumor Pathology and Pathogenesis Section, Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, FCRDC, Bldg 538 Rm 220, 21702-1201, Frederick, Maryland, USA

    Sabine Rehm

  2. ABL-Basic Research Program, NCI-RCRDC Frederick, Maryland, USA

    William Lijinsky & Barbara J. Thomas

  3. Program Resources, Inc./DynCorp., NCI-RCRDC Frederick, Maryland, USA

    Barbara H. Kasprzak

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  1. Sabine Rehm
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  2. William Lijinsky
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  3. Barbara J. Thomas
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This work was supported in part by the Department of Health and Human Services under contract number NO1-CO-74101 with ABL-Basic Research Program, Inc. and NO1-CO-74102 with Program Resources, Inc./DynCorp. The content of this publication does not necessary reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government

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Rehm, S., Lijinsky, W., Thomas, B.J. et al. Clara cell antigen in normal and migratory dysplastic Clara cells, and bronchioloalveolar carcinoma of Syrian hamsters induced by N-nitrosomethyl-n-heptylamine. Virchows Archiv B Cell Pathol 64, 181–190 (1993). https://doi.org/10.1007/BF02915111

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