Distribution of DNA adducts in the respiratory tract of rats exposed to diesel exhaust

Diesel exhaust, Inhaled chronically at high concentrations, induced tumors that were located exclusively In the peripheral lung of rats. The purpose of this study was to determine if differences in the level of DNA adducts among the regions of the respiratory tract paralleled the site of tumors. Groups of male F344/N rats were exposed 7 h/day, 5 day/wk for 12 wk to diesel engine exhaust at a soot concentration of 10 mg/m3 or were sham-exposed to air. Respiratory tract tissues were dissected and DNA was isolated from the dissected samples and analyzed for the presence of adducts using the 32P-postlabeling assay. The highest level of total DNA adducts occurred In peripheral lung tissue (∼ 18 adducts per 109 bases). About 1/4 to 1/5 the level of DNA adducts was detected in the nasal tissues as in peripheral lung. There were less than 3 adducts per 109 bases n each of the regions of the major conducting airways (.e., trachea, bronchi, axial airway). The data from this study indicate that higher levels of total DNA adducts were present In tissues where exhaust-induced tumors were located. These data suggest that DNA adduct levels in discrete locations of the respiratory tract may be good measures of the 'effective dose' of carcinogenic compounds. (author)