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American Journal of Pathology, Vol 135, 1119-1128, Copyright © 1989 by American Society for Investigative Pathology

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

M Huntrakoon, CD Menon and KS Hung
Department of Pathology and Oncology, University of Kansas Medical Center, Kansas City 66103.

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.