Preterm birth is a major medical problem of increasing incidence, and xenobiotics may contribute. The long-term goal of this project is to discover xenobiotics that contribute to preterm birth. Environmental and biological samples will be tested, and these samples will mostly come from Puerto Rico because of the unusually high incidence of preterm birth there. While nontargeted (screening) analysis will be conducted, primary attention will be given to Superfund and related contaminants, since there are many Superfund sites in Puerto Rico. Much of the analysis will be based on mass spectrometry (MS);three types of MS will be employed: (HPLC)MALDI-TOF/TOF-MS, GC-EI(EC)-TOF-MS, and HPLC-ESI-TOF-MS. We will seek to discover """"""""putative PTB-xenobiotics,"""""""" defined as xenobiotics that meet either one of the following two criteria: they correlate with preterm birth, or they do not but are common as contaminants and have a bioactivity that could contribute to this condition. The environmental samples will be tap water and ground water, including samples that have been remediated (detoxified) by electrolysis. The biological samples will be pregnancy tissues (gestational membrane, placenta), cell cultures, peripheral blood leukocytes and urine. The pregnancy tissues will come from rats and humans, and the leukocytes and urine will come from humans. One or more of four kinds of assays will be applied to each of these types of samples: 1. Direct Detection, the xenobiotic (or a laboratory derivative thereof) is directly detected in a mass spectrometer;2. DNA Adduct, the xenobiotic forms a DNA adduct in vivo that is detected by Mass Tag Profiling;3. Pro-oxidant, the xenobiotic is detected after metabolism-like oxidation in a Nucleotide Exposure Assay;4. Bioassay, the xenobiotic is detected in a bioassay with cultured cells derived from human placenta?based initially on monitoring for cytotoxicity (primary screen) and subsequently for apoptosis, genotoxicity, inflammation, and oxidative stress (secondary screen, reflecting mechanisms that could contribute to preterm birth). New or improved analytical methodology will be developed, and new combinations of methodology will be studied in this project to enhance the discovery of putative PTB-xenobiotics by these four strategies. The project, thereby, will result in generally-applicable advances in the overall field of discovering toxic xenobiotics in complex samples. Through exchange of samples, collaborative testing, and collaborative analysis of data, either directly or through the cores, this project integrates with all of the other projects in the PRoTECT program.

Public Health Relevance

Project 1 is relevant to the Program for two reasons. First, non-targeted analysis will be conducted in this project to provide a thorough search for Superfund and related contaminants that contribute to preterm birth Second, the project will bring new analytical methodology into the immature field of discovering toxic xenobiotics in complex samples.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES017198-04
Application #
8450306
Study Section
Special Emphasis Panel (ZES1-LWJ-M)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$280,612
Indirect Cost
$78,630
Name
Northeastern University
Department
Type
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115
Ferguson, Kelly K; Colacino, Justin A; Lewis, Ryan C et al. (2017) Personal care product use among adults in NHANES: associations between urinary phthalate metabolites and phenols and use of mouthwash and sunscreen. J Expo Sci Environ Epidemiol 27:326-332
Elkin, Elana R; O'Neill, Marie S (2017) Trends in Environmental Tobacco Smoke (ETS) Exposure and Preterm Birth: Use of Smoking Bans and Direct ETS Exposure Assessments in Study Designs. Chem Res Toxicol 30:1376-1383
Ferguson, Kelly K; McElrath, Thomas F; Pace, Gerry G et al. (2017) Urinary Polycyclic Aromatic Hydrocarbon Metabolite Associations with Biomarkers of Inflammation, Angiogenesis, and Oxidative Stress in Pregnant Women. Environ Sci Technol 51:4652-4660
Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica et al. (2017) Group B Streptococcus Activates Transcriptomic Pathways Related to Premature Birth in Human Extraplacental Membranes In Vitro. Biol Reprod :
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2017) Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ Int 112:243-250
Shao, Gang; Agar, Jeffrey; Giese, Roger W (2017) Cold-induced aqueous acetonitrile phase separation: A salt-free way to begin quick, easy, cheap, effective, rugged, safe. J Chromatogr A 1506:128-133
Wang, Poguang; Giese, Roger W (2017) Recommendations for quantitative analysis of small molecules by matrix-assisted laser desorption ionization mass spectrometry. J Chromatogr A 1486:35-41
Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J et al. (2017) Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy. Environ Health Perspect 125:488-494
Aung, Max T; Johns, Lauren E; Ferguson, Kelly K et al. (2017) Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study. Environ Int 104:33-40
Yuan, Ye; Meeker, John D; Ferguson, Kelly K (2017) Serum polybrominated diphenyl ether (PBDE) concentrations in relation to biomarkers of oxidative stress and inflammation: The National Health and Nutrition Examination Survey 2003-2004. Sci Total Environ 575:400-405

Showing the most recent 10 out of 137 publications