Naspinski, Christine S. (2009-05). Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures. Doctoral Dissertation. | Thesis individual record

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.

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