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Benzo(a)pyrene coated ferric oxide and aluminum oxide particles: uptake, metabolism and DNA binding in hamster pulmonary alveolar macrophages and tracheal epithelial cells in vitro.
Cheu-J; Talaska-G; Miller-M; Rice-C; Warshawsky-D
Carcinogenesis 1997 Jan; 18(1):167-175
The effects of ferric-oxide (1309371) and aluminum-oxide (1344281) particles coated with benzo(a)pyrene (50328) (BaP) on BaP uptake, metabolism, and DNA binding were examined in pulmonary alveolar macrophages (AM) and tracheal epithelial (HTE) cells obtained from Syrian-golden-hamsters. AM cultures were exposed to 0 to 2.0 milligrams (mg) of radiolabeled BaP coated particles for 24 hours. Liquid scintillation spectrometry was used to determine the intracellular uptake of BaP. AM cultures were also incubated with alpha-naphthoflavone (alpha-NF), a cytochrome-P-450 inhibitor, and carbon-monoxide (CO), an epoxide-hydrolase inhibitor. High performance liquid chromatography was used to analyze BaP metabolites. AMs were cocultured with HTE cells for 24 hours. DNA adducts in the HTE cells were examined via the phosphorus-32 postlabeling assay. The uptake of BaP was significantly higher in AMs treated with BaP coated ferric-oxide particles than in AMs treated with either BaP coated aluminum-oxide particles or BaP alone. The BaP metabolites identified included 4,5-dihydrodiol, 7,8- dihydrodiol, 9,10-dihydrodiol, 3,7-hydroxy, 9-hydroxy, 4,5-quinone, and 3,6-quinone. Metabolism was dose dependent, peaking at a BaP coated ferric-oxide dose of 1.5mg and a BaP coated aluminum-oxide dose of 2.0mg. BaP metabolism was significantly greater in AMs exposed to ferric-oxide particles than in AMs exposed to aluminum- oxide particles or BaP alone. BaP metabolism was significantly reduced in cells cotreated with alpha-NF and alpha-NF plus CO. In the presence of ferric-oxide particles, BaP metabolism was significantly higher in AMs than in HTE cells. Two major DNA adducts, 7R,8S,9S-trihydroxy-10R-(N2-deoxyguanosyl-3'-phosphate) 7,8,9,10-tetrahydrobenzo(a)pyrene and 7S,8R,9R-trihydroxy-10S-(N2- deoxyguanosyl-3'-phosphate) 7,8,9,10-tetrahydrobenzo(a)pyrene, were found. DNA binding in HTE cells was greater in the presence of BaP coated ferric-oxide particles than in the presence of either BaP coated aluminum-oxide particles or BaP alone. Treatment with both inhibitors significantly reduced the relative adduct labeling in the HTE cells. The authors conclude that ferric-oxide can enhance the uptake, metabolism, and DNA binding capabilities of BaP.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Grants-other; Alveolar-cells; DNA-adducts; Cellular-uptake; Cell-metabolism; Aluminum-oxides; Iron-oxides; Dose-response; Exposure-levels
Environmental Health University of Cincinnati 3223 Eden Avenue Cincinnati, OH 45267-0056
1309-37-1; 1344-28-1; 50-32-8
Issue of Publication
Pulmonary-system-disorders; Other Occupational Concerns; Grants-other
University of Cincinnati, Cincinnati, Ohio
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division