Tissue distribution of the tobacco-specific carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and its metabolites in F344 rats
The tissue distribution of the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in the F344 rat was studied by whole-body autoradiography and high-performance liquid chromatography. The results of the wholebody autoradiography experiments indicate that the substance is able to freely cross biological membranes and reach all tissues of the body. A high level of tissue-bound metabolites occurred in the mucosa of the ethmoturbinates, in the lung, and the liver, which are the targets for the carcinogenicity of NNK in F344 rats. However, tissue-bound radioactivity was also present in non-target tissues such as the lateral nasal gland(Steno's gland), the tracheal mucosa, and the mucosa of the nasopharyngeal duct. A high level of unbound radioactivity occurred in the preputial gland, submaxillary and adrenal glands, and the urinary and gastrointestinal systems. High localization of unbound radioactivity was observed in the stomach lumen not only after p.o. but also after i.v. administration of NNK. Analysis of extracts of the stomach contents by high-performance liquid chromatography indicated that, due to their basicity, NNK and its metabolites were trapped in the gastric juice and later reabsorbed from the intestinal tract. Analysis of unbound metabolites in various tissues and in the urine after i.v. or p.o. administration of (carbonyl-/sup 14/C)NNK indicated metabolism and excretion of products resulting from alpha-carbon hydroxylation, carbonyl reduction, and pyridine N-oxidation of NNK. In vitro autoradiography experiments showed that NNK is metabolized in the mucosa of the ethmoturbinates, the lung, and the liver, suggesting that the tumors are induced by metabolites formed locally in the target tissues. In the lung, the labeling was higher in the bronchial tree than in the lung parenchyma.
- Research Organization:
- Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York
- OSTI ID:
- 6094736
- Journal Information:
- Cancer Res.; (United States), Vol. 43:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
NITROSAMINES
METABOLISM
TISSUE DISTRIBUTION
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
CARCINOGENESIS
CELL MEMBRANES
LUNGS
MUCOUS MEMBRANES
PHARYNX
RATS
TOBACCO PRODUCTS
TRACER TECHNIQUES
AMINES
ANIMALS
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
DISTRIBUTION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques