Autoradiographic observations on the distribution and metabolism of N?-/14C/nitrosonornicotine in mice

Abstract

The fate of the weak base N′-nitrosonornicotine (2′-¹⁴C-labeled) has been studied in mice. Whole-body autoradiography showed that the radioactivity was rapidly distributed throughout the body, which probably reflects an ability of the non-protonated compound to freely pass biological membranes and distribute evenly in the intra- and extracellular tissue water. Metabolites which were firmly bound to tissue macromolecules — retained throughout the observational period (24 h) — were present in the tracheobronchial and nasal mucosa, the liver, the submaxillary and sublingual salivary glands and the esophagus. Radioactivity in the lacrimal gland, the gastrointestinal contents, the urinary bladder, and the gallbladder seems to be related to excretion of the substance and/or its metabolites. A binding to the melanin in the eye and hair was observed in vivo and in vitro. Experiments with mice pretreated with diethyldithiocarbamate and nialamide showed that these substances partially inhibited the metabolism of N′-/¹⁴C/nitrosonornicotine. CO₂ was not recovered in the breath during the 4 h following the administration of N′-/¹⁴C/nitrosonornicotine.