SRI Authors: Jason D. White
White, J. D., Leib, R. D., & Manning-Bog, A. B. (2014, 10-14 August). Building a breathprint: Biomarkers of exposure due to the toxicant trochloroethylene. Paper presented at the ACS National Meeting & Exposition, San Francisco, CA.
Exposure to environmental toxins is a significant risk factor for the development of Parkinson’s disease (PD), a neurodegenerative disease that afflicts over 1 million Americans. Motor symptoms and diagnosis of this disorder typically occur after significant neuronal degeneration of the nigrostriatal pathway has manifested, but the underlying pathophysiological changes are known to occur much earlier. Assessment of biomarkers following toxicant exposure has the potential not only to identify at-risk populations, but also to aid in diagnosis of the disease in its earliest stages, inform preventive strategies, and provide information that might help researchers develop treatments that could slow or even halt PD progression.
One such environmental contaminant, trichloroethylene (TCE), is a component commonly utilized in metal degreasers and in the dry cleaning and painting industries. Approximately 50 million pounds of TCE are released annually into the US environment, where it persists in groundwater sources because of improper disposal.1,2 TCE is detected in 30% of US drinking water supplies at concentrations between 1 and 100 ppm.3 After ingestion, TCE may partially metabolize into other toxic compounds, including chloral hydrate, and trichloroacetic acid. These can be absorbed in various cells and tissues, including neurons. In a recent study of 99 twins, the twin exposed to TCE was significantly more likely to develop PD than the unexposed twin.4 We are developing a non-invasive breath test to build a biomarker panel of volatile organic compounds (VOCs) for exposure monitoring and evaluation of neuronal degeneration indicative of PD. Initial experiments utilize exhaled samples from a pre-clinical mouse model exposed to TCE. Breath environment samples are collected from each mouse and analyzed using laser-ionization time-of-flight mass spectrometry (LI-TOF-MS). This approach results in high sensitivity with a very short analysis time and can identify unknown VOC formulae in the absence of external standards. Our pilot studies indicate that we can detect TCE and other VOCs in the breath environment that are indicative of neuronal degeneration. Pending studies will investigate the relationship between toxicant exposure and VOCs with known markers of nigrostriatal damage in animal models which can be correlated to VOCs from breath samples of human PD patients. Thus, these studies may have clinical significance because of their potential to enable a new, non-invasive collection and analysis technology for early detection of PD. A novel diagnostic tool such as this might also allow screening for other environmental exposures and lead to remediation of toxins linked with PD and other diseases.