Superfund Research Program
Discovery of Xenobiotics Associated with Preterm Birth
Project Leader: Roger W. Giese
Grant Number: P42ES017198
Funding Period: 2010-2020
Final Progress Reports
Studies and Results
Urinary Sulfateome. Sulfation is a major attachment reaction in the metabolism of many xenobiotics (environmental chemicals in the body), to help their removal into the urine. Considering this, and the fact that sulfates are readily detected by mass spectrometry (MS), the urinary sulfateome (collection of sulphated chemicals in urine) is a good place to search for xenobiotics that contribute to preterm birth. Dr. Giese and his research team are increasing the coverage of the urinary sulfateome via use of a porous extraction paddle prior to detection by MS. To date they have extended the coverage of the higher mass sulfateome in pregnancy urine by 5-fold in this way, and further coverage is in progress.
Ionic Tagging. The research team has continued its studies of 2-sulfobenzoic anhydride (SBA) as an ionic tagging reagent to increase detection sensitivity by MS, leading to a manuscript in press for publication in Rapid Communications in Mass Spectrometry. They have studied detection of phenols with this reagent, an important class of xenobiotics and xenobiotic metabolites. While many phenols give a low response by MS, tagging with SBA overcomes this problem. The research team has also developed a new ionic tag to improve the detection of carboxy metabolites (e.g. glucuronides, mercapturic acids) in urine, and as well as DNA damage in placenta, by environmental chemicals. This will further increase their ability to discover xenobiotics that increase risk of preterm birth.
Chemical Deconjugation. Dr. Giese and his research team have developed the first mild, universal, chemical procedure to convert chemical metabolites back to chemicals, since can make it easier to discover or confirm environmental chemicals in a biosample. This reaction takes place at room temperature, and overcomes the problem that enzymes for this purpose are not universal.
The project is significant in seeking to reduce the incidence of preterm birth, a major health problem. Also, the project is advancing technology in general for chemical analysis in the area of human exposure to chemicals. Humans are always exposed to mixtures, and discovery chemical analysis, which is this this project's approach, is a good way to characterize such exposures. This in turn can improve risk assessment for exposure of humans to environmental chemicals.