Metabolism of a nasal carcinogen, phenacetin, in the mucosa of the upper respiratory tract.

The metabolism of [ethyl-14C]phenacetin in the rat and rabbit respiratory tract was studied. As shown by whole-body autoradiography, a selective binding of radioactivity occurred in the mucosa of the rat respiratory tract 5 min after an i.v. injection of [ethyl-14C]phenacetin. Microautoradiography showed that tissue-bound radioactivity was present in the epithelium of the nasal and tracheo-bronchial mucosa and in subepithelial glands in the olfactory mucosa. In vitro experiments showed that the mucosa of the rat and rabbit respiratory tract had a marked ability to metabolize [ethyl-14C]phenacetin, as determined by 14CO2 formation and binding of radioactivity to the mucosa. The results indicate that in situ metabolism of phenacetin in the nasal mucosa may play a role in the pathogenesis of phenacetin-induced tumours in the nasal region of rats.