Localization of bound metabolites in the respiratory tissues and oesophagus by high-resolution microautoradiography in Fischer 344 rats treated with N'-nitrosonornicotine.
High-resolution microautoradiography for detection of bound radioactivity in Fischer 344 rats given a single subcutaneous dose of 3H-N'-nitrosonornicotine (3H-NNN) showed a labelling of the olfactory region of the nose, which was restricted to the secretory cells of the glands of the lamina propria mucosae (Bowman's glands). In the oesophagus, bound radioactivity was present in the squamous epithelium, most marked in the middle and superficial cell layers. The olfactory nasal mucosa and the oesophagus are targets for the carcinogenicity of NNN in Fischer 344 rats. Our results indicate that the labelled cells in these tissues are the principal sites in which NNN is activated to alkylating species, and these cells may also be the ones that undergo malignant transformation. Bound radioactivity was also found in the lung (mainly in the Clara cells of the bronchi and bronchioles) and in the trachea (preferentially in the mucous cells), although NNN does not induce tumours in the lung or trachea of the rats. Why covalent binding of metabolites to cellular macromolecules is not correlated to carcinogenesis at these sites is not known.
Tjälve
H
H
Department of Pharmacology and Toxicology, Swedish University Agricultural Sciences, Uppsala.
Castonguay
A
A
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics*; D004947:Esophagus / Q000032:analysis*; D009602:Nitrosamines / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344 / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*
D002273:Carcinogens; D009602:Nitrosamines; C008655:N'-nitrosonornicotine