Metabolism and macromolecular covalent binding of (/sup 14/C)-1-nitropyrene in isolated perfused and ventilated rat lungs

Journal Article · Sat Sep 01 04:00:00 EDT 1984 · Cancer Res.; (United States)

OSTI ID:6199392

Bond, J A; Mauderly, J L

The purpose of this study was to quantitate l-nitropyrene (1-NP) metabolism and macromolecular covalent binding in the isolated perfused rat lung. Rat lungs were perfused with 2, 5, or 24 microM (/sup 14/C)-1-NP for 90 min. Tidal volume and dynamic lung compliance were monitored throughout the perfusion to document the ventilatory pattern and the decay of tissue elasticity. Perfusate was sampled periodically throughout the experiment and analyzed for 1-NP metabolites with high-performance liquid chromatography. In all experiments, both dynamic lung compliance and tidal volume declined in a nearly linear manner and were approximately 60% of the initial value at the end of 90 min of perfusion. At all concentrations of (/sup 14/C)-1-NP tested, less than 5 to 6% of the total amount of (/sup 14/C)-1-NP added was metabolized in lungs from control and phenobarbital (PB)-treated rats. Lungs from control and PB- and 3-methylcholanthrene (3-MC)-treated rats metabolized (/sup 14/C)-1-NP to oxidized, reduced, and conjugated metabolites. The major metabolites were 3-, 6-, and 8-hydroxynitropyrene. Treatment of rats with PB resulted in a 60% increase in the total metabolism of (/sup 14/C)-1-NP, whereas treatment of rats with 3-MC resulted in a 10-fold increase in the rate of metabolism of (/sup 14/C)-1-NP when compared to controls. Conjugate hydrolysis studies indicated that the water-soluble metabolites from lungs of control and PB- and 3-MC-treated rats consisted of hydroxynitropyrene glucuronides and hydroxynitropyrene sulfate conjugates. Quantities of /sup 14/C covalently bound to lung macromolecules after 90 min of perfusion from lungs of control and PB-treated rats were 0.06 to 0.21 nmol equivalents/g lung. However, in lungs from 3-MC-treated rats, there was a 20-fold increase in quantities of 14C covalently bound when compared to lungs from either control or PB-treated rats.

• Research Organization: Inhalation Toxicology Research Inst., Albuquerque, NM
• OSTI ID: 6199392
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:9; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
550501 -- Metabolism-- 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.
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARCINOGENS
CONDENSED AROMATICS
DYNAMIC FUNCTION STUDIES
HYDROCARBONS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LUNGS
MAMMALS
METABOLISM
METABOLITES
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PERFUSED ORGANS
PHYSIOLOGY
POLYCYCLIC AROMATIC HYDROCARBONS
PYRENE
RATS
REACTION KINETICS
RESPIRATION
RESPIRATORY SYSTEM
RODENTS
TRACER TECHNIQUES
VERTEBRATES