Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment and are generated by many sources. Though the potential of PAH-rich mixtures to cause health effects has been known for almost a century, there are still unanswered questions about the levels of PAHs in the environment, the potential for human exposure to PAHs, the health effects associated with exposure, and how genetic susceptibility influences the extent of health effects in individuals. The first objective of this research was to quantify concentrations of PAHs in samples of settled house dust collected from homes in Azerbaijan, China, and Texas. The trends of PAH surface loadings and percentage of carcinogenic PAHs were China > Azerbaijan > Texas, indicating that the risk of health effects from exposure to PAHs in house dust is highest in the Chinese population and lowest in the Texas population. PAHs in China and Azerbaijan were derived mainly from combustion sources; Texas PAHs were derived from unburned fossil fuels such as petroleum. The second objective of this research was to investigate the effect of pregnane X receptor (PXR) on the genotoxicity of benzo[a]pyrene (BaP). BaP treatment resulted in significantly lower DNA adduct levels in PXR-transfected HepG2 cells than in parental HepG2 cells. Total GST enzymatic activity and mRNA levels of several metabolizing enyzmes were significantly higher in cells overexpressing PXR. These results suggest that PXR protects cells against DNA damage by PAHs such as BaP, possibly through a coordinated regulation of genes involved in xenobiotic metabolism. The third objective of this research was to investigate biomarkers of exposure in house mice (Mus musculus) exposed to PAH mixtures in situ. Mice and soil were collected near homes in Sumgayit and Khizi, Azerbaijan. Mean liver adduct levels were significantly higher in Khizi than in Sumgayit. Mean lung and kidney adduct levels were similar in the two regions. The DNA lesions detected may be a combination of environmentally-induced DNA adducts and naturally-occurring I-compounds. PAHs were present at background levels in soils from both Khizi and Sumgayit. It appears that health risks posed to rodents by soil-borne PAHs are low in these two areas