Influence of the dose levels of cocarcinogen ferric oxide on the metabolism of benzo[a]pyrene by pulmonary alveolar macorphages in suspension culture

Journal Article · Fri Jan 01 04:00:00 EST 1993 · Journal of Toxicology and Environmental Health; (United States)

OSTI ID:7284326

Greife, A L ^[1]; Warshawsky, D ^[2]

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1. National Institute for Occupational Safety and Health, Cincinatti, OH (United States)
2. Univ. of Cincinatti Medical Center, OH (United States)

The concurrent administration of a cocarcinogenic carrier particle such as ferric oxide (Fe[sub 2]O[sub 3]) and the polycyclic aromatic hydrocarbon lung carcinogen benzo[a]pyrene (BaP) results in a decreased latency and an increased incidence in the production of lung tumors in hamsters compared to the administration of BaP alone. The pulmonary alveolar macrophage (AM), the primary lung defense cell, has been shown to endoctyze BaP, metabolize BaP to a more biologically active form, and then release metabolites. Therefore, a study was undertaken to determine in a dose-response manner the effect of AM phagocysosis of a carrier particle (Fe[sub 2]O[sub 3]) on the metabolism of a carcinogen (BaP) and on the production of reactive oxygen. The AM were lavaged from hamsters and cultured in suspension (2.5 [times] 10[sup 6] cells/vial) with bAp (62.5 NMOL, [sup 14]c labeled) alone or adsorbed onto 0.5, 1.0, or 2.0 mg Fe[sub 2]O[sub 3] in the presence of cytochrome c. Following separate ethyl acetate extractions of the AM and medium, the metabolites were isolated by high-performance liquid chromatography (HPLC) and quantified by liquid scintillation spectrometry. The production of superoxide anions was monitored by the reduction of cyctochrome c. Concurrent exposure of AM to BaP-coated Fe[sub 2]O[sub 3] resulted in a significant increase in the amount of BaP metabolites and superoxide anions produced with dose of Fe[sub 2]O[sub 3]. The following metabolites and superoxide anions produced with dose of Fe[sub e]O[sub 3]. The following metabolites were identified in both the medium and the AM: 9,10-dihydrodiol, 7,8-dihydrodiol, 4,5-dihydrodiol, 9-hydroxy, 3-hydroxy, and 3,6 quinone. 44 refs., 5 figs., 2 tabs.

• OSTI ID: 7284326
• Journal Information: Journal of Toxicology and Environmental Health; (United States), Journal Name: Journal of Toxicology and Environmental Health; (United States) Vol. 38:4; ISSN 0098-4108; ISSN JTEHD6
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BODY
CARCINOGENESIS
CHALCOGENIDES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
HAMSTERS
HYDROCARBONS
IRON COMPOUNDS
IRON OXIDES
KINETICS
LUNGS
MAMMALS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
REACTION KINETICS
RESPIRATORY SYSTEM
RESPONSE MODIFYING FACTORS
RODENTS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES