Metabolism of tobacco-specific nitrosamines by cultured rat nasal mucosa

Journal Article · Thu Sep 01 00:00:00 EDT 1983 · Cancer Res.; (United States)

OSTI ID:5621711

Brittebo, E B; Castonguay, A; Furuya, K; Hecht, S S

The metabolism of two nasal carcinogens, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was investigated using cultured nasal septa of F344 rats. The explants were cultured with 14C-labeled N-nitrosamines, and unbound metabolites present in the medium were quantitated by high-performance liquid chromatography. The results indicated that the mucosa of the nasal septum had a marked capacity to metabolize NNN and NNK to hydroxylated products which were released into the culture media. Extensive activation by alpha-carbon hydroxylation of NNN (preferentially 2'-carbon hydroxylation) and NNK was observed, whereas no deactivation by pyridine N-oxidation could be detected. Microautoradiographic studies of explants showed that binding of radioactivity occurred preferentially in the respiratory and olfactory epithelia and in the subepithelial glands of the nasal mucosa. The results suggest that reactive metabolites of NNN and NNK are formed within the target tissue rather than being transported from the liver to the nasal mucosa. The results also show that the culture of nasal septa can be used to ascertain the role of the nasal mucosa in the activation of nasal-specific carcinogens.

• Research Organization: Department of Pharmacology, Faculty of Veterinary Medicine, Uppsala Biomedical Centre, Sweden
• OSTI ID: 5621711
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 43:9; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AEROSOLS
ALKALOIDS
AMINES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZINES
AZOLES
BODY
BODY AREAS
CARBON 14 COMPOUNDS
CELL CULTURES
CHROMATOGRAPHY
COLLOIDS
DISPERSIONS
DRUGS
FACE
HEAD
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MEMBRANES
METABOLISM
METABOLITES
MUCOUS MEMBRANES
NICOTINE
NITROSAMINES
NITROSO COMPOUNDS
NOSE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PYRIDINES
PYRROLES
PYRROLIDINES
RATS
RESIDUES
RESPIRATORY SYSTEM
RODENTS
SEPARATION PROCESSES
SMOKES
SOLS
TOBACCO SMOKES
VERTEBRATES