Rat lung benzo(a)pyrene metabolism following three days continuous exposure to 0. 6 ppm ozone
Changes in the extent and pattern of benzo(a)pyrene metabolism were investigated in lungs isolated from rats following ozone exposures that are associated with the proliferation of alveolar and bronchiolar epithelia. Radiolabel incorporation into metabolic products were determined at the end of 60 min perfusions with 50-55 nmol of (6-3H) (7, 10-14C) benzo(a)pyrene (BaP), which in unexposed lungs resulted in a total BaP utilization of 0.77 +/- 0.05 nmol (14C) BaP/h/lung, recovered bound to tissue macromolecules (12%), as tissue and perfusate ethyl acetate-soluble products (59%), and as perfusate water-soluble conjugates (29%). Total metabolism at the sixth position of the BaP molecule was indicated by a 3H2O production of 0.07 +/- 0.01 nmol BaP/h per lung, that resulted in the formation of quinones (33%), acid-hydrolysable (40%) and acid-resistant (27%) water-soluble products, indicated by 14C- minus 3H-labelling. Ozone-exposed lungs demonstrated an increased total (14C) BaP utilization to 3.05 +/- 0.05 nmol/h/lung. Although BaP metabolism to all products was increased, the proportion of metabolism involving the 6th position was enhanced from 10% to 25% of total BaP utilization, which was accounted for by relative increases in tissue retained quinones and in perfusate acid-hydrolysable conjugates. These data demonstrated that quinone formation represents a major pathway of lung polycyclic aromatic hydrocarbon metabolism that is greatly enhanced in lungs with proliferating epithelia associated with oxidant exposure.
- Research Organization:
- Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (USA)
- OSTI ID:
- 6578704
- Journal Information:
- Res. Commun. Chem. Pathol. Pharmacol.; (United States), Vol. 60:3
- Country of Publication:
- United States
- Language:
- English
Similar Records
Metabolism and macromolecular covalent binding of (/sup 14/C)-1-nitropyrene in isolated perfused and ventilated rat lungs
Effects of the co-carcinogen catechol on benzo(a)pyrene metabolism and DNA adduct formation in mouse skin
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
METABOLISM
EPITHELIUM
CELL PROLIFERATION
OZONE
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
LUNGS
METABOLITES
QUINONES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
RESPIRATORY SYSTEM
RODENTS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques