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© 1992 Oxford University Press

research-article

A study of tobacco carcinogenesis XLVIII. carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison)

Nils Koppang 1 2, Abraham Rivenson 3, Albrecht Reith 4, Hans K. Dahle 2, Øystein Evensen 1 and Dietrich Hoffmann 3 5

1National Veterinary Institute N-0033 Oslo 1, Norway
2Norwegian College of Veterinary Medicine N-0033 Oslo 1, Norway
3American Health Foundation Valhalla, NY 10595, USA
4Norwegian Radium Hospital and Institute for Cancer Research 0310 Oslo 3, Norway

5To whom requests for reprints should be sent

During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.


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