Cocarcinogenicity of particles in coculture system.
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio 1995 Jul; :1-64
The effects of particles on the metabolism of benzo(a)pyrene (50328) (BaP) and on the formation of BaP-DNA adducts were investigated in- vitro. Alveolar macrophages (AM), from male Syrian-Golden-hamsters were incubated with BaP at 5 microgram amounts either alone or with BaP coated respirable size iron-oxide (1309371) (Fe2O3) or aluminum- oxide (1344281) (Al2O3) in concentrations from 0.5 to 2.0 milligrams per plate. The release of diol, phenol, quinone, and total BaP metabolites was significantly increased in the AM treated with Fe2O3 coated BaP when compared to AM exposed to BaP alone or to Al2O3 coated BaP. Also increased in these same Fe2O3 treated macrophages was the formation of BaP 7,8-diol. When alpha-naphthoflavone was coadministered, the BaP metabolism was significantly reduced. A similar reduction was noted on treatment with the epoxide-hydrolase inhibitor cyclohexene-oxide. The author concludes that particles enhance BaP metabolism through the modulation of P450 1A1 or a1A2 and epoxide-hydrolase. Results also indicated that Fe2O3 enhanced the formation of total DNA adduct in the hamster tracheal epithelial cells. The author suggests that enhanced BaP metabolism and DNA adduct formation by Fe2O3 particles results from an increased uptake of BaP and the modulation of the P450 enzymatic pathway.
NIOSH-Grant; Cancer; Pyrenes; Cell-cultures; Carcinogens; DNA-adducts; Metabolic-study; Mammalian-cells; Iron-oxides
Environmental Health University of Cincinnati 3223 Eden Avenue Cincinnati, OH 45267-0056
50-32-8; 1309-37-1; 1344-28-1
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NTIS Accession No.
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio
University of Cincinnati, Cincinnati, Ohio