Formation of tissue-bound N'-nitrosonornicotine metabolites by the target tissues of Sprague-Dawley and Fisher rats.

The distribution and metabolism of N' -[14C] nitrosonornicotine ([14C]NNU) was studied in Sprague-Dawley and Fisher rats, in which NNN induces tumours preferentially of the nasal cavity and the oesophagus. After i.v. injections of [14C] NNN, a localization of tissue-bound metabolites weas found in the mucosa of the nasal cavity and oesophagus. These tissues were also found to have a capacity to form tissue-bound metabolites from NNN in vitro. These data suggest that in situ metabolic activation of NNN plays an important role in the pathogenesis of the NNN-induced tumours of the nasal cavity and the oesophagus in the rat.