Biomarkers of exposure to complex environmental mixtures

Maternal exposure to genotoxic chemicals may produce a variety of adverse birth outcomes. Depending on the dose and duration of exposure, adverse birth outcomes can range from premature or low-birth weight, to congenital abnormalities including neural tube defects (NTDs). The research described in this dissertation focused on several rural counties in Shanxi province, China. Shanxi has one of the highest rates of NTDs in the world. In 2005, the incidence of NTDs in the study counties ranged from 8 to 24 cases per 1,000 births. While some of these birth defects are likely to be related to nutrition, it is also suggested that environmental factors play a significant role. One such factor includes polycyclic aromatic hydrocarbon (PAH) exposure as a result of combustion of coal for indoor heating and cooking. Human populations in Shanxi depend heavily on coal as their main source of energy. This study determined the concentrations of PAHs in house dust, venous blood and placenta of study participants. Dust was collected from homes in the study site. Carcinogenic PAH levels in dust collected from kitchen floors ranged from 12 to 2,000 ?g/m2. The genotoxic potential of dust was confirmed by shortterm bioassays. Median concentrations of total PAHs in placenta from children born with NTDs were elevated compared to matched controls and appeared to be associated with the risk of having a child with a NTD. Tobacco smoking was not associated with elevated levels of PAH biomarkers in this study population. Levels of bulky DNA adducts in placenta have also been quantified using 32P-postlabeling. Adduct levels do not appear to be significantly different between cases and controls and were not associated with deletions in enzymes GSTM1 or GSTT1. These data suggest that children born with NTDs may be at increased risk due to exposure to genotoxic PAHs. Studies with a larger number of subjects are needed to further elucidate the relationship between PAH exposure and adverse birth outcomes.