Pulmonary metabolism of dibenz(a,j)acridine: A carcinogenic heterocyclic aromatic: Final report for period September 1, 1982-June 30, 1986
The metabolism of the carcinogenic N-heterocyclic aromatic, dibenz(a,j)-acridine (DBA) was investigated in the isolated perfused lung (IPL) preparation. A significantly increased rate of metabolism was observed for DBA in benzo(a)-pyrene (BaP) and DBA-pretreated animals. This resulted in marked increases in conjugation, in particular sulfates and thioethers, and the distribution of conjugates and total metabolites in blood and lung. When Fe/sub 2/O/sub 3/ was coadministered with DBA to the IPL, the rate of metabolism was significantly decreased with respect to control experiments. This resulted in increased distributions of sulfate and thioether conjugates in blood. Spectroscopic analyses and microsomal enzyme analyses were used in the characterization of the four metabolites identified in the lung. The major nonconjugated metabolite was the 3,4 dihydrodiol of DBA and the three minor metabolites were the 4 and 3 phenol of DBA and a dihydroxy compound of DBA. The results indicate that in the lung DBA is metabolized in a manner similar to that of BaP but different from that of dibenzo-(c,g)carbazole. It is, therefore, apparent that the metabolism of N-heterocyclic aromatics are related to the aromaticity of the heteroatom-containing ring and the solubility of compound, as well as the specific enzymes responsible for activation of the compound. 115 refs., 78 figs., 24 tabs.
- Research Organization:
- Cincinnati Univ., OH (USA). Dept. of Environmental Health
- DOE Contract Number:
- AC02-82ER60076
- OSTI ID:
- 6470799
- Report Number(s):
- DOE/ER/60076-3; ON: DE87012995
- Resource Relation:
- Other Information: Portions of this document are illegible in microfiche products
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ACRIDINES
FLUORESCENCE SPECTROSCOPY
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
METABOLISM
AZAARENES
METABOLITES
CARBON 14 COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
GLUCURONIDE CONJUGATES
INTRATRACHEAL ADMINISTRATION
INTRAVENOUS INJECTION
IRON OXIDES
LUNGS
METABOLIC ACTIVATION
PHENOLS
RABBITS
REVIEWS
SULFATES
TRACER TECHNIQUES
ANIMALS
AROMATICS
AZINES
BODY
CHALCOGENIDES
CHROMATOGRAPHY
DOCUMENT TYPES
EMISSION SPECTROSCOPY
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INJECTION
INTAKE
IRON COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PYRIDINES
RESPIRATORY SYSTEM
SEPARATION PROCESSES
SPECTROSCOPY
SULFUR COMPOUNDS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques