Polycyclic Aromatic Hydrocarbon-DNA Adducts in White Blood Cells and Urinary 1-Hydroxypyrene in Foundry Workers

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/ m3), was considerably lower than in a previous study at this foundry (≤50 to 200 ng/m3) (F. P. Perera ef al., Cancer Res., 48: 2288–2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 junol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19-to 20-fold range in the values within each of the three exposure groups. PAH-DNA adducts showed an increasing trend, with exposure from 5.2 to 6.1 to 9.6 adducts/108 nucleotides in the low-, medium-, and high-exposure groups, respectively (P 0.08). The three exposure groups did not significantly differ from each other by analysis of variance (P 0.23). There was a 10- to 35-fold range in PAH-DNA adducts within exposure groups, reflecting the interindividual variability in this molecular response to PAH exposure. The correlation (r) between the two markers was 0.15 (P = 0.37). These results indicate that even at relatively low levels of benzo(a)pyrene (approximately 30-fold lower than in the previous study), we continue to observe a dose-response relationship between external exposure and the biologically effective dose of PAH.