Project Overview

Summary:

Dr. Yao-Zhong Liu at Tulane University’s School of Public Health & Tropical Medicine, Global Biostatistics and Data Science, was awarded an RFP-VI grant at $596,256 to conduct the RFP-VI project titled, “Impact of Oil Spill to Human Lung Health: Next Generation Sequencing and Mouse Model Based Analyses”. The project consisted of 1 principal investigator (Liu); 2 co-PIs (Drs. Charles Miller, Gilbert Morris); 1 research scientist (Shigeki Saito); 1 research staff member (Yan Zhuang); 1 PhD student (Sudurika Mukhopadhyay); and 1 master student (YiFei Wang).

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) (1, 2) spilled and dispersants (1.8 million gallons) applied (3, 4) and the large number of workers (>50,000) involved in the cleaning operation.

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 (5), long-lasting airway oxidative stress (6), and systemic genetic effects (7).

To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, RNA-seq analyses (8, 9) 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 (8), 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 (8, 9) 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 (10). 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 (8, 9). 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.

Research Highlights

Dr. Liu’s research, which included 0 outreach products and activities, resulted in 1 scientific conference presentation, 1 peer-reviewed publication (shown below) to date and 3 datasets submitted to the GoMRI Information and Data Cooperative (GRIIDC), which are available to the public.

The Impact of the Deepwater Horizon Oil Spill upon Lung Health-Mouse Model-Based RNA-Seq Analyses. Liu YZ, Miller CA, Zhuang Y, Mukhopadhyay SS, Saito S, Overton EB, Morris GF. Int J Environ Res Public Health. 2020 Jul 29;17(15):E5466. doi: 10.3390/ijerph17155466. PMID: 32751227

Significant outcomes of their research (all related to GoMRI Research Theme 5) are highlighted below.

1. Toxicological and carcinogenic impacts of Corexit 9527 and BP crude oil to the lung system are supported using mouse models.
2. Corexit 9527 may have a major impact to the lung system through DNA damage, which may introduce novel somatic mutations and lead to cancer development in the long run. This was demonstrated in the wild-type B6 mice of both genders.
3. BP crude oil’s effects on the lung system may involve proinflammatory activities, as demonstrated in the wild-type B6 mice.
4. Both oil and Corexit 9527 may accelerate tumorigenesis, which was observed in the K-ras mice.
5. Overall, our project has provided strong evidence supporting long-term public health consequence of the BP oil spill to the lung health for local residents and those workers involved in the cleanup.

References:

1. Machlis GE, McNutt MK. Disasters. Scenario-building for the Deepwater Horizon oil spill. Science. 2010;329(5995):1018-9. Epub 2010/08/28. doi: 10.1126/science.1195382. PubMed PMID: 20798302.
   
   
2. Crone TJ, Tolstoy M. Magnitude of the 2010 Gulf of Mexico oil leak. Science. 2010;330(6004):634. Epub 2010/10/12. doi: 10.1126/science.1195840. PubMed PMID: 20929734.
   
   
3. EPA. EPA response to BP spill in the Gulf of Mexico Dispersants. Monitoring and assessment of dispersants used in the BP response 2011. Available from: https://archive.epa.gov/emergency/bpspill/web/html/dispersants.html.
   
   
4. Wise J, Wise JP, Sr. A review of the toxicity of chemical dispersants. Rev Environ Health. 2011;26(4):281-300. Epub 2011/01/01. doi: 10.1515/reveh.2011.035. PubMed PMID: 22435326; PMCID: PMC6730675.
   
   
5. Zock JP, Rodriguez-Trigo G, Rodriguez-Rodriguez E, Souto-Alonso A, Espinosa A, Pozo-Rodriguez F, Gomez FP, Fuster C, Castano-Vinyals G, Anto JM, Barbera JA. Evaluation of the persistence of functional and biological respiratory health effects in clean-up workers 6 years after the prestige oil spill. Environ Int. 2014;62:72-7. Epub 2013/11/05. doi: 10.1016/j.envint.2013.09.020. PubMed PMID: 24184661.
   
   
6. Rodriguez-Trigo G, Zock JP, Pozo-Rodriguez F, Gomez FP, Monyarch G, Bouso L, Coll MD, Verea H, Anto JM, Fuster C, Barbera JA, Group SE-PS. Health changes in fishermen 2 years after clean-up of the Prestige oil spill. Ann Intern Med. 2010;153(8):489-98. Epub 2010/08/25. doi: 10.7326/0003-4819-153-8-201010190-00279. PubMed PMID: 20733177.
   
   
7. Laffon B, Fraga-Iriso R, Perez-Cadahia B, Mendez J. Genotoxicity associated to exposure to Prestige oil during autopsies and cleaning of oil-contaminated birds. Food Chem Toxicol. 2006;44(10):1714-23. Epub 2006/07/04. doi: 10.1016/j.fct.2006.05.010. PubMed PMID: 16814914.
   
   
8. Liu YZ, Zhang L, Roy-Engel AM, Saito S, Lasky JA, Wang G, Wang H. Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells. Gene. 2017;602:16-23. Epub 2016/11/21. doi: 10.1016/j.gene.2016.11.028. PubMed PMID: 27866042; PMCID: PMC5191957.
   
   
9. Liu YZ, Roy-Engel AM, Baddoo MC, Flemington EK, Wang G, Wang H. The impact of oil spill to lung health--Insights from an RNA-seq study of human airway epithelial cells. Gene. 2016;578(1):38-51. Epub 2015/12/23. doi: 10.1016/j.gene.2015.12.016. PubMed PMID: 26692141; PMCID: PMC5072127.
   
   
10. Morris GF, Danchuk S, Wang Y, Xu B, Rando RJ, Brody AR, Shan B, Sullivan DE. Cigarette smoke represses the innate immune response to asbestos. Physiol Rep. 2015;3(12). doi: 10.14814/phy2.12652. PubMed PMID: 26660560.

 Proposal Abstract - RFP-VI PI Yao-Zhong Liu