||Formation of DNA Adducts in Rat Lung Following Chronic Inhalation of Diesel Emissions, Carbon Black and Titanium Dioxide Particles.
Gallagher, J. ;
Heinrich, U. ;
George, M. ;
Hendee, L. ;
Phillips, D. H. ;
||Health Effects Research Lab., Research Triangle Park, NC. ;Fraunhofer-Inst. fuer Toxikologie und Aerosolforschung, Hanover (Germany, F.R.). ;Integrated Lab. Systems, Research Triangle Park, NC. ;Institute of Cancer Research, Surrey (England). Haddow Labs.
DNA adducts ;
Carbon black ;
Titanium dioxide ;
Diesel fuels ;
Air pollutants ;
Aromatic polycyclic hydrocarbons ;
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The objective of the study was to determine whether the polycyclic aromatic hydrocarbons (PAH), nitro-PAH or other polycyclic organic matter adsorbed to diesel particles induces the formation of DNA adducts in the lung when compared to particles with little or no adsorbed organic matter in conjunction with a chronic inhalation cancer study. Wistar rats were exposed to diesel emissions (7.5 mg/cu m) for 2 months, 6 months and 2 years time points and 2 years to carbon black (11.3 mg/cu m) and TiO2 particles (10.4 mg/cu m) to compare tumorigenic response and DNA adduct formation in the lung. Two versions of the (32)P-postlabeling assay for the detection of DNA adducts were used to identify nirated- or aryl- amine adducts formed relative to other PAH adducts based on the demonstrated sensitivity of these adducts to nuclease P1 treatment. Total adduct levels were determined as well as two specific individual adducts, one major adduct (1) which migrated outside the zone and a nuclease P1 sensitive adduct (2) detected inside the zone. Adduct 1 increased significantly over time in the controls but decreased markedly at the two year time points regardless of particle type. These data suggest that long term contact with these particles may result in a cell of proliferative response, enhanced degradation of I-compounds not related to cell proliferation, and or synthesis of I-compounds, irrespective of the differences in organic content associated with the three particle types.