Completed: Discovery of Xenobiotics Associated with Preterm Birth

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Significance: The project, an integral part of the PROTECT center, is significant in seeking to reduce the incidence of preterm birth, a major health problem.  Also, the project is significant in advancing technology in general for nontargeted chemical analysis in the area of human exposure to chemicals.  Humans are always exposed to mixtures, and nontargeted chemical analysis is a good way to characterize such exposures.  This in turn can improve risk assessment for human exposure to chemical exposures.


The long term goal of this project is to discover xenobiotics that contribute to preterm birth, relying on nontargeted chemical analysis by mass spectrometry.  The project is increasing the sensitivity, scope, and qualitative capability of current methods for nontargeted chemical analysis, and applying these improved methods to biological and environmental samples. The project, for example, conducts nontargeted analysis of urine samples, and studies the hypothesis that preterm urines in Puerto Rico contain a different exposome (overall in vivo environmental chemical exposure) than term urines. A large volume (0.5 gallon) of urine as an accumulation of early morning voids is being collected from each pregnant woman, which then is extracted with a porous extraction paddle (stirring “reversed tea bag” filled with particulate adsorbents).  This new technique yields a convenient repository sample (the bag of adsorbents) for shipment, storage, and analysis of aliquots. The project is also using the technique to identify pollutants in ground and tap water samples in Puerto Rico, and pollutant degradation products formed when these samples are remediated in Project 5 by electrolysis. Other activities in the project involve advances in the analysis of DNA adducts as biomarkers of exposure for testing DNA adducts in human placenta (placental DNA adducts might contribute to preterm birth); improved technology for deconjugation of xenobiotics (to improve the scope of nontargeted chemical analysis); and advances in ionic tagging (also a way to facilitate nontargeted chemical analysis).
To date, the project has invented a Porous Extraction Paddle (PEP) device that is a porous nylon bag filled with solid phase extraction particles, where the bag is rigidified by a metal cage that, in turn, is attached to a stirring motor. This provides a convenient way to extract a large volume of liquid (urine or water) at a remote location, while minimizing contamination.   For urine, the large volume as a series of voids enables an integrated measure of exposure, which is more meaningful than data from a spot urine.   The PEP has been submitted by Northeastern University as a regular patent application. The PEP promises to become, beyond this project,  a new tool for sampling by epidemiologists, allowing them to conveniently collect large-volume urine specimens for prospective cohort studies, similar to the PROTECT cohort.   We have extended our prior method for nontargeted chemical analysis of DNA adducts (markers of DNA damage by chemicals) to polar DNA adducts, and this has led to several publications.  A new DNA adduct, 6-oxo-thymine, and also one of benzoquinone, has been discovered.   We have discovered a new reaction technique that provides universal deconjugation of sulfate and glucuronide metabolites under mild conditions.  The use of enzymes for this purpose is compromised since no enzyme acts universally.  Scientists have tried to achieve such a reaction technique for many years without success.

Specificity and sensitivity for detecting a given class of chemicals can be achieved by appropriate derivatization.  This can facilitate nontargeted chemical analysis. We are advancing ionic tags for this purpose. For example, we have improved the ability of the ionic tag, 2-sulfobenzoic anhydride, to detect phenolic compounds.  Some phenols in the environment are of concern as endocrine disrupters.

— L-R: Gang Shao, Roger Giese, Poguang Wang —

Roger Giese, Project Leader

Director, Environmental Cancer Research Program & Professor of Chemistry and Biomedical Science, Northeastern University

Poguang Wang, Investigator

Principal Research Scientist, Department of Pharmaceutical Sciences and Barnett Institute, Northeastern University

Company Sponsors

PROTECT acknowledges generous support from the following companies for this project:
  • Accu-Seal Corporation, San Marcos, CA, has provided a medical-grade bag sealer which we are using for sample preparation.
  • Sigma Aldrich Corporation, St. Louis, MO, is providing a diversity of chromatographic packings, also for use in sample preparation.
  • Thermo-Fisher, Pittsburgh, PA, is providing a discounted reagent.
  • Yankee Containers, North Haven, CT, donated transport vessels for samples between Boston and Puerto Rico.
  • Industrial Fabrics Corm, Minneapolis, MN, donated nylon netting.
  • Affymetrix, Santa Clara, CA, donated a modified nucleotide standard.

Learn more about the team by checking out the Project 3 video!