GoMRI
Investigating the effect of oil spills
on the environment and public health.
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Funding Source: Year 8-10 Research Grants (RFP-VI)

Project Overview

Impact of Oil Spill to Human Lung Health: Next Generation Sequencing and Mouse Model Based Analyses

Principal Investigator
Tulane University- School of Public Health & Tropical Medicine
Global Biostatistics and Data Science
Member Institutions
Tulane University School of Medicine, Tulane University- School of Public Health & Tropical Medicine

Abstract:

The year 2017 marked the seventh anniversary of the Deepwater Horizon oil spill, the largest man-made disaster in the history of petroleum industry. The sheer scale of this disaster is marked by its long duration (lasting for ~3 months), the gigantic volume of crude oil (210 million gallons) spilled and dispersants (1.8 million gallons) applied and the large number of workers (>50,000) involved in the cleaning operation (1, 2).

 

The full impacts of the disaster to the environment and marine and human lives have yet to be fully unveiled. Specifically, the long term health impacts of the BP oil spill to the >50,000 workers involved in the cleaning operation have not been well characterized and followed up, although limited data on other smaller scale oil spills (e.g., the Prestige oil spill) did suggest that involvement in oil spill cleaning operations may cause persistent respiratory symptoms (3), long-lasting airway oxidative stress (4), and systemic genetic effects (5-8).

 

To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, RNA-seq analyses (9, 10) were performed on human airway epithelial cells (the BEAS-2B cells) treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, transcriptomic perturbations of the treated cells at KEGG pathway levels were identified (10), with a pattern of change towards carcinogenesis marked by upregulation of ribosomal biosynthesis, protein processing, Wnt signaling, neurotrophin signaling and insulin signaling pathways under 9527 or 9500+oil treatments. The PI’s current proteomics analysis on the same cells also indicated upregulation of cancer promoting genes and downregulation of cancer suppressive genes of the treated cells, further supporting the carcinogenic potential of the treated cells as revealed by RNA-seq analysis.

 

A major limitation of the PI’s recent RNA-seq studies (9, 10) is that the findings from the studied BEAS- 2B cells under submerged culture may not perfectly mirror the in vivo responses to the chemicals in humans. Therefore, to address this limitation, the PI proposes to adopt mouse models that have been well established for studying in vivo effects of smoking and asbestos by the co-PI, Dr. Morris (11-14). This new system on the mouse models allows the investigators to test the in vivo effects of oil/dispersants regarding carcinogenesis. The general hypothesis is that upon respiratory exposure to oil/dispersant there will be a higher carcinogenic potential of lung tissue in the mice. To test this hypothesis the following 2 aims will be achieved:

Aim 1: To profile and confirm the existence of molecular signatures of carcinogenesis through RNA-seq analysis of the mouse model (the B6 mice) treated with instilled oil/dispersants.

Aim 2: To determine if respiratory exposure to oil/dispersants accelerates tumorigenesis in lung tumor bearing mice (the K-Ras mice).

 

The proposed analyses will provide compelling evidence to validate the PI’s group’s recent findings on carcinogenic potential of oil and dispersants on the lung system (10). This will address the key research theme of “impact of oil spills on public health”, as requested by GoMRI. The project will clarify if there are indeed harmful effects of crude oil and dispersants to human lung health for those workers involved in the oil spill cleaning process and even for those working in the presence of crude oil fumes on a daily basis. The evidence provided, if positive, will serve as a solid foundation for new legislation protecting oil industry workers and will provide the rationale for developing/using safer oil dispersants with low carcinogenicity.


This research was made possible by a grant from The Gulf of Mexico Research Initiative.
www.gulfresearchinitiative.org