Effects of a cocarcinogen, ferric oxide, on the metabolism of benzo(a)pyrene in the isolated perfused lung
An isolated perfused New Zealand rabbit lung preparation was used to investigate the effects of a cocarcinogen, ferric oxide (Fe/sub 2/O/sub 3/), on the metabolism of benzo(a)pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban settings. (/sup 14/C)-BaP was administered intratracheally to an isolated perfused lung (IPL) preparation with and without Fe/sub 2/O/sub 3/ after intraperitoneal pretreatment of the whole animal with BaP or intratracheal pretreatment of the whole animal with Fe/sub 2/O/sub 3/ and/or BaP. BaP and its metabolites were isolated from serial blood samples up to 180 min after administration of (/sup 14/C)BaP to the IPL. BaP and its metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by chromatographic techniques and liquid scintillation counting. Fe/sub 2/O/sub 3/ pretreatment to the whole animal or administration of Fe/sub 2/O/sub 3/ to the IPL altered BaP metabolism by the perfused lung. Fe/sub 2/O/sub 3/ pretreatment to the whole animal resulted in an increase in the total rate of appearance of metabolites of BaP in the blood, while Fe/sub 2/O/sub 3/ administration to the IPL resulted in a decrease in the total rate of appearance of BaP metabolites in the blood and inhibited the effect of pretreatment. These data suggest that pulmonary exposure to a known cocarcinogen, Fe/sub 2/O/sub 3/, in the presence of BaP results in increased production of dihydrodiols of BaP, which may be further metabolized to the ultimate carcinogenic form(s) of BaP. Therefore, Fe/sub 2/O/sub 3/ can enhance the metabolic activation of BaP by the lung, as well as act as a carrier for penetration and retention of BaP in the lung. 49 references, 6 tables.
- Research Organization:
- Univ. of Cincinnati Medical Center, OH
- OSTI ID:
- 5885183
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 14:2-3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENESIS
METABOLIC ACTIVATION
BRONCHI
CARBON 14 COMPOUNDS
CARCINOMAS
CHROMATOGRAPHY
EXPERIMENTAL DATA
INTRATRACHEAL ADMINISTRATION
IRON OXIDES
LUNGS
MACROPHAGES
METABOLITES
PERFUSED ORGANS
RABBITS
RETENTION
SCINTILLATION COUNTING
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
AROMATICS
BODY
CHALCOGENIDES
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
COUNTING TECHNIQUES
DATA
DISEASES
HYDROCARBONS
INFORMATION
IRON COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NEOPLASMS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PATHOGENESIS
PHAGOCYTES
RESPIRATORY SYSTEM
SEPARATION PROCESSES
SOMATIC CELLS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques