# POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION

> **NIH NIH P42** · BAYLOR COLLEGE OF MEDICINE · 2021 · $16,050

## Abstract

Project Summary
 The major objective of this project is to provide research and training experience to Dr. Guobin Xia as a
KC Donnelly Externship trainee. He will visit Dr. Bruce Hammock’s laboratory at UC Davis for his externship.
Supplemental oxygen is frequently given to preterm infants and adults with pulmonary insufficiency, but
hyperoxia contributes to lung injury, which in turn leads to bronchopulmonary dysplasia (BPD) in preterm
infants and ARDS in adults. Environmental chemicals such as polycyclic aromatic hydrocarbons (PAHs),
which are present in Superfund sites are known to increase the risk of preterm birth (PTB) in women living near
Superfund sites. In this project, Dr. Guobin Xia, a postdoctoral associate in my laboratory, in collaboration with
Dr. Bruce Hammock (UC Davis), will test the hypothesis that maternal exposure of wild type (WT) mice to the
PAH benzo[a]pyrene (BP) on gestational days 16-19, followed by postnatal hyperoxia (80% oxygen) for 14
days will lead to exacerbation of alveolar simplification of newborn mice on postnatal day (PND) 15 , and that
combined treatment of newborn mice with soluble epoxide hydrolase (sEH) inhibitor (sEHI) 1-
trifluoromethoxyphenyl-3-(1-propionyl-4-yl)urea (TPPU) and oxygen will lead to protection against lung injury,
compared to vehicle-treated mice. He hypothesizes that linoleic acid metabolites such as leukotoxin diols
[dihydroxyoctadecenoic acids (DiHOMEs)] are elevated in mice exposed to hyperoxia, and this phenomenon is
exacerbated in mice pretreated with BP, leading to increased lung injury. We postulate that mice treated with
TPPU will show protection against lung injury. We propose the following Specific Aim: 1. To test the
hypothesis that prenatal exposure of wild type (WT) (C57BL/6J) mice to the PAH BP will result in exacerbation
of lung injury and alveolar simplification following postnatal hyperoxia, and this effect will be attenuated in
newborn mice treated with sEH inhibitor, TPPU. Timed pregnant WT mice will be treated orally with corn oil
(vehicle control) (CO) or BP (15 mg/kg), on gestational days 16-19, and newborns will be delivered at full term
(day 21). These doses are relevant to human exposures, and to women living near Superfund sites. The
newborns will be divided into two groups, with one group receiving TPPU only every other day by i.p for 14
days, and other group will be given the vehicle CO. These mice will be further divided in to 2 groups, one
group to be maintained in room air, and the other exposed to hyperoxia (80% O2) for 14 days, and animals will
be sacrificed on postnatal day (PND) 15 or PND 30. Lung injury and abnormal lung alveolarization will be
assessed. We will also assess cytokine levels, levels of oxylipins, including leukotoxin diols, will measured in
lungs by UPLC/MS-MS on PND15. If successful, leukotoxin diols have the potential of being developed as
novel biomarkers of BPD.

## Key facts

- **NIH application ID:** 10382017
- **Project number:** 3P42ES027725-02S2
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** BHAGAVATULA MOORTHY
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,050
- **Award type:** 3
- **Project period:** 2020-02-28 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382017

## Citation

> US National Institutes of Health, RePORTER application 10382017, POLYCYCLIC AROMATIC HYDROCARBONS: ULTRASENSITIVE DETECTION, EARLY LIFE EXPOSURES-CLINICAL OUTCOMES (PRETERM BIRTHS, CHRONIC LUNG DISEASE, AND NEUROCOGNITIVE DEFICITS), PREVENTION AND REMEDIATION (3P42ES027725-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10382017. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*