Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman

Journal Article · Sun Mar 01 04:00:00 EST 1987 · Cancer Res.; (United States)

OSTI ID:6863259

Brittebo, E B

The metabolism and binding of the analgetic drug (ring-/sup 3/H)phenacetin in the nasal mucosa were studied in vitro and in vivo in male Sprague-Dawley rats. As shown by whole-body and light microscopic autoradiography there was an irreversible binding of metabolites to the glands of Bowman in the olfactory mucosa after high but not after low doses of (/sup 3/H)phenacetin. In the other tissues, the distribution of radioactivity was not changed when the dose was increased. Autoradiography of (/sup 3/H)-acetaminophen showed no preferential uptake of radioactivity in the olfactory mucosa. At incubation of nasal septa with (/sup 3/H)phenacetin in vitro, a binding of metabolites to the glands of Bowman was observed indicating that the metabolism occurred in situ. In rats, glutathione (GSH) depleted by pretreatment with phorone, there was a binding to the glands of Bowman in the olfactory mucosa also after a trace dose of (/sup 3/H)phenacetin. Addition of GSH decreased the irreversible binding of (/sup 3/H)phenacetin metabolites that occurred in 9000 X g nasal mucosa supernatants incubated with (/sup 3/H)phenacetin. There was a moderate decrease in the level of nonprotein sulfhydryl groups, mainly GSH, in the olfactory mucosa after administration of 100-300 mg/kg phenacetin. Collectively, these data suggest that phenacetin is metabolized and subsequent to GSH depletion, bound preferentially in the glands of Bowman. The data also suggest that in situ metabolic activation and binding of phenacetin in the rat nasal mucosa at high doses may play a role in the pathogenesis of the nasal tumors induced by high doses of phenacetin in the rat.

• Research Organization: Swedish Univ. of Agricultral Sciences, Uppsala
• OSTI ID: 6863259
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 5; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIPYRETICS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BODY
BODY AREAS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FACE
HEAD
IN VITRO
IN VIVO
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
METABOLIC ACTIVATION
METABOLISM
METABOLITES
MUCOUS MEMBRANES
NOSE
ORGANIC COMPOUNDS
RATS
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
VERTEBRATES