LOCALIZATION OF [NITROSONORNICOTINE-C-14 IN TISSUES OF THE MOUSE

Abstract

Male C57BL/6J mice were given i.v. injections of 7 mg (.apprx. 4 .mu.Ci) of N''-[pyrrolidine-2-14C]nitrosonornicotine per kg and frozen by immersion in dry ice: hexane at 0.1, 0.33, 1, 3, 9 and 24 h after injection. The mice were processed for whole-body autoradiography without allowing thawing or the use of any solvents; sagittal sections of the frozen mice were freeze dried and placed on X-ray film to reveal areas of localization of radioactivity. At 6 min after administration, radioactivity was highest in liver, kidney, parotid gland, nasal epithelium, melanin and contents of lower stomach; there was very little radioactivity at this time interval in bronchial epithelium. At later time intervals, there was increasing radioactivity in bronchial and nasal epithelium and sublingual and submandibular duct epithelium. Twenty-four hours after administration, virtually the only radioactivity remaining in the entire body was in the epithelium of the nasal cavity, bronchi, esophagus and salivary glands and also in melanin, liver, proximal tubules of the kidney and preputial gland. The autoradiographs are interpreted to reveal that most of the radioactivity is eliminated by renal and hepatic secretion and that metabolites are retained only at sites of carcinogenic action. The specificity of accumulation in nasal, bronchial, esophageal and salivary duct epithelium may be due to receptor-directed interactions and suggests that other compounds might block this accumulation. [The most abundant carcinogen that has been identified to date in tobacco smoke or its condensate is N''-nitrosonornicotine.].