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. 1989 Dec;135(6):1119–1128.

Diethylnitrosamine-induced pulmonary endocrine cell hyperplasia and its association with adenomatosis and adenocarcinoma in rabbits.

M Huntrakoon 1, C D Menon 1, K S Hung 1
PMCID: PMC1880490  PMID: 2596573

Abstract

Pulmonary endocrine cells are suspected of being the precursors for small cell carcinoma of the lung (SCCL). The purpose of this study was to determine whether Diethylnitrosamine (DEN) can induce SCCL in rabbits. New Zealand white rabbits were injected subcutaneously with 20 mg/kg body weight of DEN, twice per week, starting when they were 1 week old. Controls received saline vehicle only. The animals were sacrificed 6 to 8.5 months after the first injection and lung tissues were processed for light microscopy. Using serotonin (5-HT) as a marker for the endocrine cells, tissue sections were stained immunohistochemically by the avidin-biotin complex method. In both control and DEN-treated animals, serotonin-immunoreactive cells organized into neuroepithelial bodies (NEBs). There was an apparent increase in the size, number, and stainability of NEB in DEN-injected animals. A majority of these NEBs were localized in the alveolar duct region. Small foci of adenomatosis and well-differentiated adenocarcinomas, which sometimes coexisted with hyperplastic pulmonary endocrine cells, were also found in the DEN-treated rabbits.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BENSCH K. G., GORDON G. B., MILLER L. R. ELECTRON MICROSCOPIC AND BIOCHEMICAL STUDIES ON THE BRONCHIAL CARCINOID TUMOR. Cancer. 1965 May;18:592–602. doi: 10.1002/1097-0142(196505)18:5<592::aid-cncr2820180508>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  2. Baylin S. B., Mendelsohn G. Ectopic (inappropriate) hormone production by tumors: mechanisms involved and the biological and clinical implications. Endocr Rev. 1980 Winter;1(1):45–77. doi: 10.1210/edrv-1-1-45. [DOI] [PubMed] [Google Scholar]
  3. Bensch K. G., Corrin B., Pariente R., Spencer H. Oat-cell carcinoma of the lung. Its origin and relationship to bronchial carcinoid. Cancer. 1968 Dec;22(6):1163–1172. doi: 10.1002/1097-0142(196811)22:6<1163::aid-cncr2820220612>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  4. Cho T., Chan W., Cutz E. Distribution and frequency of neuro-epithelial bodies in post-natal rabbit lung: quantitative study with monoclonal antibody against serotonin. Cell Tissue Res. 1989 Feb;255(2):353–362. doi: 10.1007/BF00224118. [DOI] [PubMed] [Google Scholar]
  5. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  6. Ito T., Kitamura H., Inayama Y., Kanisawa M. 4-Nitroquinoline 1-oxide-induced pulmonary endocrine cell hyperplasia in Syrian golden hamster. Jpn J Cancer Res. 1986 May;77(5):441–445. [PubMed] [Google Scholar]
  7. Kleinerman J., Marchevsky A. M., Thornton J. Quantitative studies of APUD cells in airways of rats. The effects of diethylnitrosamine and NO2. Am Rev Respir Dis. 1981 Oct;124(4):458–462. doi: 10.1164/arrd.1981.124.4.458. [DOI] [PubMed] [Google Scholar]
  8. Lauweryns J. M., Peuskens J. C. Neuro-epithelial bodies (neuroreceptor or secretory organs?) in human infant bronchial and bronchiolar epithelium. Anat Rec. 1972 Mar;172(3):471–481. doi: 10.1002/ar.1091720301. [DOI] [PubMed] [Google Scholar]
  9. Linnoila R. I., Becker K. L., Silva O. L., Snider R. H., Moore C. F. Calcitonin as a marker for diethylnitrosamine-induced pulmonary endocrine cell hyperplasia in hamsters. Lab Invest. 1984 Jul;51(1):39–45. [PubMed] [Google Scholar]
  10. Linnoila R. I. Effects of diethylnitrosamine on lung neuroendocrine cells. Exp Lung Res. 1982 Nov;3(3-4):225–236. doi: 10.3109/01902148209069655. [DOI] [PubMed] [Google Scholar]
  11. Linnoila R. I., Nettesheim P., DiAugustine R. P. Lung endocrine-like cells in hamsters treated with diethylnitrosamine: alterations in vivo and in cell culture. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5170–5174. doi: 10.1073/pnas.78.8.5170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Redick M. L., Hung K. S. Quantitation of pulmonary neuroepithelial bodies in pre- and postnatal rabbits. Cell Tissue Res. 1984;238(3):583–587. doi: 10.1007/BF00219875. [DOI] [PubMed] [Google Scholar]
  13. Reznik-Schüller H. M., Hague B. F., Jr Autoradiography in fetal golden hamsters treated with tritiated diethylnitrosamine. J Natl Cancer Inst. 1981 Apr;66(4):773–777. [PubMed] [Google Scholar]
  14. Reznik-Schüller H. Ultrastructural alterations of nonciliated cells after nitrosamine treatment and their significance for pulmonary carcinogenesis. Am J Pathol. 1976 Dec;85(3):549–554. [PMC free article] [PubMed] [Google Scholar]
  15. Reznik-Schüller H. Ultrastructure of nitrosoheptamethyleneimine-induced lung tumors in European hamsters. Am J Pathol. 1978 Oct;93(1):45–52. [PMC free article] [PubMed] [Google Scholar]
  16. Schuller H. M., Becker K. L., Witschi H. P. An animal model for neuroendocrine lung cancer. Carcinogenesis. 1988 Feb;9(2):293–296. doi: 10.1093/carcin/9.2.293. [DOI] [PubMed] [Google Scholar]
  17. Sidhu G. S. The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature. Am J Pathol. 1979 Jul;96(1):5–20. [PMC free article] [PubMed] [Google Scholar]
  18. Tateishi R., Ishikawa O. The effect of N-nitrosobis(2-hydroxypropyl)amine on pulmonary neuroepithelial cells in Syrian golden hamsters. Am J Pathol. 1985 May;119(2):326–335. [PMC free article] [PubMed] [Google Scholar]

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