| Summary: | 博士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 107 === Background: Exposomics is an important methodology in environmental health research. Recently, a branching paradigm, the Public Health Exposome Approach, focuses on the impact of exposures on the overall health of a population within a particular region. This dissertation focuses on the exposomics study of residents living near No. 6 Naphtha Cracking Complex, the largest petrochemical complex in Taiwan, and aim to clarify the association between exposure levels, metabolome, and early health effect biomarkers.
Material and Methods: We classified 273 study subjects as high exposure group (children aged 9-15 N=43; elderly aged > 55 N=77) and low exposure group (children N=75; elderly N=78) by the distance from their homes to the complex, and urinary levels of exposure biomarkers vanadium (V) and polycyclic aromatic hydrocarbon (PAHs) metabolite 1-hydroxypyrene (1-OHP). We analyzed (1) external exposures: distance from their homes to main emission points of the complex, road area surrounding homes, and ambient levels of V and PAHs at homes using previously established models; (2) internal exposures: urinary levels of exposure biomarkers, arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), mercury (Hg), lead (Pb), vanadium (V), manganese (Mn), copper (Cu), strontium (Sr), thallium (Tl), and 1-OHP; (3) metabolome: urine metabolomics was analyzed using two dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS), and serum metabolomics and lipidomics were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qTOFMS); (4) early health effects: urinary levels of oxidative stress biomarkers, and serum acylcarnitines. We applied “meet-in-the-middle” approach to identify potential intermediate biomarkers connecting exposures with early health effects, and pathway analysis to find biological mechanisms affected by exposure to multiple pollutants.
Results: In both children and elderly subjects, high exposure group lived closer to main emission points of the complex, had elevated ambient levels of V and PAHs at home locations, and increased urinary exposure biomarkers and oxidative stress biomarkers compared to low exposure group. Urine metabolomics identified age-dependent biological pathways that associated multiple pollutants exposure with increased oxidative stress, including tryptophan metabolism in children, and serine, glycine, and threonine metabolism in elderly subjects. In addition, potential exposure biomarkers decane, dodecane, and tridecane were identified in both children and elderly subjects. Serum metabolomics found 10 potential metabolites possibly linking increased exposure to IARC group 1 carcinogens (As, Cd, Cr, Ni) and group 2 carcinogens (V, Hg, PAHs) with elevated oxidative stress and deregulated serum acylcarnitines. Purine metabolism was identified as the possible mechanism affected by children’s exposure to carcinogens. Serum lipidomics results in children also showed significant difference between high and low exposure groups. We found 21 lipids associated with multiple industrial pollutants exposure, including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, and phosphatidylinositols. All four types of lipids were associated with urinary oxidative stress biomarkers and/or serum acylcarnitines.
Conclusion: Public health exposome approach could be used in a large petrochemical industry influenced region to identify vulnerable populations, and understand how multiple industrial pollutants exposure are affecting critical biological mechanisms, leading to early health effects that may be precursors to chronic and acute diseases. Urine metabolomics analyzed via GC-based method could be used to identify children and elderly as vulnerable populations in regions influenced by a large petrochemical industry, and found age-dependent pathways linking multiple exposures to increased oxidative stress. Serum metabolomics analyzed via LC-based method could be used to find biological pathways affected by multiple industrial carcinogenic pollutants exposure in children and adolescents, that could be linked to cancer-related early health effects. Serum lipidomics analyzed via LC-based method could be used to identify in children and adolescents exposed to multiple industrial pollutants, lipid profile changes that have been implicated in liver dysfunctions. Based on our findings, we suggest significant reduction of petrochemical industrial emissions from the complex to decrease multiple pollutants exposure and metabolic abnormalities, and continued follow up on of residents’ health. This dissertation also attests the application of exposomics as a public health research tool, in the investigation of current and potential health impacts of industrial pollution on nearby residents, providing information for future identification of novel personalized health indicators and exposure biomarkers, and establishment of individual risk index.
|
|---|
