Metastasis to the F344 Rat Pancreas from Lung Cancer Induced by 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)- 1-butanol, Constituents of Tobacco Products

Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in car...

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Bibliographic Details
Published in:Toxicologic pathology 2018-02, Vol.46 (2), p.184-192
Main Authors: Kovi, Ramesh C., Johnson, Charles S., Balbo, Silvia, Hecht, Stephen S., O’Sullivan, M. Gerard
Format: Article
Language:English
Subjects:
Animals
Carcinogens - metabolism
Carcinogens - toxicity
Carcinoma - chemically induced
Carcinoma - secondary
Lung Neoplasms - chemically induced
Lung Neoplasms - pathology
Male
Nicotiana - chemistry
Nitrosamines - metabolism
Nitrosamines - toxicity
Pancreatic Neoplasms - secondary
Rats
Rats, Inbred F344
Stereoisomerism
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Summary:Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused by tobacco products. NNK and racemic NNAL are reported to induce lung and pancreatic tumors in rats. The carcinogenicity in Fischer 344 rats of NNK, NNAL, and its enantiomers (R)-NNAL and (S)-NNAL has been studied recently, and all test compounds induced significant numbers of lung tumors. We report here the detailed histopathological and immunohistochemical characterization of these tumors and their aggressive nature as shown by their metastasis locally and to the pancreas. The spectrum of treatment-related histopathological findings comprised pulmonary alveolar/bronchiolar (A/B) epithelial hyperplasia, A/B adenomas, and A/B carcinomas. A/B carcinomas frequently exhibited local invasion/metastasis within the mediastinum and thoracic cavity and distant metastasis to the pancreas that was confirmed by immunohistochemistry using the lung-specific markers prosurfactant protein-C and club (Clara) cell-10. Our observation regarding metastasis to the pancreas was an important, and unexpected, finding in this study both for the experimental animal model and potential human relevance.
ISSN:0192-6233
1533-1601
DOI:10.1177/0192623317751573