عنوان

Effects of ferric oxide and aluminum oxide on the metabolism of benzo(a)pyrene and DNA adduct formation

TLpq304174987

انگلیسی

Effects of ferric oxide and aluminum oxide on the metabolism of benzo(a)pyrene and DNA adduct formation

[Thesis]

C. J. Cheu

University of Cincinnati

1995

139

D.S.E.H.

University of Cincinnati

1995

The respiratory tract is a common route for entry of toxic materials from modern urban and working environments. Feusd\rm\sb2O\sb3usd and Alusd\rm\sb2O\sb3usd particles are widely encountered in the occupational settings. Benzo(a)pyrene, a well-characterized environmental carcinogen, is also frequently coexposed with particles in the occupational settings. The aim of this study is to assess the role of particles on the modulation of metabolism of BaP by AM and the binding of BaP metabolites to the DNA of target epithelial cells. AM from male Syrian Golden hamsters were incubated (usd3\times10\sp6usd/plate) with BaP (5 mug) alone or BaP (5 mug)-coated respirable size Feusd\rm\sb2O\sb3usd and Alusd\rm\sb2O\sb3usd particles from 0.5 mg to 2.0 mg. The metabolic profiles from media and cells at 24 hr indicate that the release of dihydrodiols, phenols, quinones and total BaP metabolites was significantly greater with Feusd\rm\sb2O\sb3usd compared to BaP alone or Alusd\rm\sb2O\sb3usd (p < 0.05). Our results also have shown that the uptake of BaP into the AM at 24 hr is greater in the treatment of BaP-coated Feusd\rm\sb2O\sb3usd than that of BaP alone or BaP-coated Alusd\rm\sb2O\sb3.usd Coadministration of 7,8-benzoflavone (5 muM), an inhibitor of cytochrome P-450s (1A1 and 1A2), significantly reduced the BaP metabolism in BaP-coated Feusd\rm\sb2O\sb3usd and Alusd\rm\sb2O\sb3usd treatments. Cyclohexene oxide (CO, 10 M), an inhibitor of epoxide hydrolase, had the similar effect as 7,8-benzoflavone on the reduction of BaP metabolism. These data suggest that Feusd\rm\sb2O\sb3usd particles enhance the metabolism of BaP in AM is associated with the increased uptake of BaP and the modulation of P-450 dependent pathways. DNA adduct profiles in HTE cells which were cocultured with AM indicate that BaP-coated Feusd\rm\sb2O\sb3usd enhance the formation of total DNA adduct in the HTE compared to the treatment of BaP-coated Alusd\rm\sb2O\sb3usd or BaP alone. Two adducts (adduct-1 and 2), tentatively characterized by co-migration with (+)-anti-BPDE-dG and ()-anti-BPDE-dG standards respectively, appeared in different proportions in different treatments. P-450 dependent and independent pathways were thought to contribute to the formation of adduct-1 and adduct-2, respectively. The relative adducted labeling (RAL) of each adduct is higher in HTE in the treatment of BaP-coated Feusd\rm\sb2O\sb3usd than that of BaP-coated Alusd\rm\sb2O\sb3usd or BaP alone. Both inhibitors, usd\alphausd-NF and CO, reduced the RAL of adducts in the HTE under different treatments, including BaP alone, BaP-coated Feusd\rm\sb2O\sb3usd and BaP-coated Alusd\rm\sb2O\sb3.usd Our data suggest that the enhancement of BaP metabolism as well as BaP-related DNA adduct formation by Feusd\rm\sb2O\sb3usd particles is associated with P-450 dependent metabolic activation pathway, and possibly P-450 independent processes.

aluminum oxide

benzo(a)pyrene

Health and environmental sciences

iron oxide

Occupational safety

Toxicology

C. J. Cheu

p

[Thesis]

276903

a

Y