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EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS
Citation:
Sampson, D. A., J. Kongerud, J Scott, J Inmon, D. Peden, AND J Gallagher. EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS. Presented at AACR, New Orleans, LA, March 24-28, 2001.
Description:
The overall aim of this study is to determine (using a nasal challenge model) the effect of diesel exhaust particles (DEP) on nasal responses including induction of inflammation, immune changes and DNA damage. We are also examining how treatment of DEP with ozone (oz-DEP)modify these effects. Studies show that DEP increases nasal IgE production. Other studies show that polycyclic aromatic hydrocarbons (PAH) appear to play a central role in the effect of DEP on allergic inflammation. The specific aim of the study reported here, evaluates whether: 1) nasal derived-PAH DNA adducts are useful biomarkers of diesel exposure 2) normalizing the DNA adduct levels to reflect the number of various cell types detected in the samples will indicate cell type(s) involved in modulating DNA adduct levels. Normal healthy subjects undergo a bilateral nebulized nasal lavage and then are challenged bilaterally with either saline(control), 0.3mg of DEP or oz-DEP. Oz-DEP were prepared by exposure to 0.1 ppm ozone x48 hr. Nasal lavage samples are obtained preexposure then 4 and 96 hrs after challenge. Cell analysis is complete for n=15/treatment group. DNA isolation and analysis is underway. The number of cells obtained for the DEP-exposed range from 8.0x10e4-3,0x10e6: Mean values for total cell number (saline group)= 4.6x10e5 +/ 4.2x10e5. Despite high interindividual variability at 4hr (ie+/-152%), intra-individual variability was markedly lower (ie,+/- 52%). R2 values (reflecting associations between an individual's repeat cell measurements at two time points) improved after the initial nasal lavage in the diesel exposed individuals (r2=0.19 vs 0.59).Cell types enumerated in the nasal lavage included squamous epithelial, mononuclear, PMN, eosinophils, ciliated epithelial cells. An increase in the percent of PMN/ml relative to controls in the diesel group was observed at 4hr and persisted over a 96 hr interval. Taken together our analyses will provide mechanistic and exposure effects data for an important air pollution source. This abstract does not necessarily represent EPA policy.