Abstract
We used a transcriptomic approach to interrogate the effects of a saline-accommodated fraction from the Macondo 252 well (MC252) oil and Corexit dispersants on lung tissue. Wild-type C57BL/6 male and female mice were exposed on days 0, 7 and 13 by oropharyngeal aspiration to saline accommodated fractions (SAF) of crude oil from the Macondo (MC252) well, Corexit 9500, Corexit 9527, 9500+oil and 9527+oil or a saline solution as the vehicle control. These treatments did not cause overt toxicity, with the exception of the Corexit exposures which caused brief weight loss after the first exposure. On day 14, total RNA was isolated from the left lung for RNA-seq analyses. KEGG-pathway-based differential expression revealed that Corexit 9527 elicited the strongest changes involving the upregulation of 19 KEGG pathways (FDR < 0.10), followed by Corexit 9500 with the upregulation of seven pathways (FDR < 0.10). As an important signature, pathways related to a response to DNA damage (e.g., p53 signaling and mismatch repair) dominate those upregulated by Corexit 9527 and Corexit 9500. In addition, pro-inflammatory pathways (e.g., cytokine-cytokine receptor interaction, IL-17 signaling pathway and TNF signaling pathways) were upregulated selectively in oil-treated male mice. Surprisingly, oil + dispersant combinations caused lesser effects than the individual treatments at the transcriptomic level. Overall, these findings support potential genotoxicity, inflammation and cell death due to dispersant or oil exposures. Similar exposures to lung tumor bearing K-RasLA1 mice provided evidence for tumor promotion by oil and Corexit dispersant treatments. Our mouse RNA-seq analyses may be relevant to the pulmonary health hazards of MC252 oil and dispersants experienced in exposed populations.
Highlights
Introduction19 September 2010), when the well was formally declared sealed, approximately 210 million US gallons of crude oil spilled [1,2] and 1.84 million US gallons of oil dispersants were applied [3,4]
The Deepwater Horizon oil spill was the largest marine oil spill in the history of the petroleum industry and one of the largest environmental disasters in American history [1,2].During the period of ~5 months, when the well was formally declared sealed, approximately 210 million US gallons of crude oil spilled [1,2] and 1.84 million US gallons of oil dispersants were applied [3,4].Approximately 50,000 workers were involved in the cleanup during and after the spill
Previous experiments indicated that the Corexit 9500+oil and Corexit 9527+oil saline accommodated fractions (SAF) displayed similar toxicity curves with BEAS-2B cells in culture and that at 1/100 dilution of both solutions was toxic [27]
Summary
19 September 2010), when the well was formally declared sealed, approximately 210 million US gallons of crude oil spilled [1,2] and 1.84 million US gallons of oil dispersants were applied [3,4]. 50,000 workers were involved in the cleanup during and after the spill. The formation of aerosols containing oil and dispersants on the sea surface at the site of oil spill [5] could present a public health threat. Short- and long-term health effects might occur from inhaling oil and dispersant chemicals. Respiratory irritation symptoms have been reported in both cleanup workers [6] and the local women of southern Louisiana following the oil spill [7]. Evidence of genotoxic effects that persisted 5–6 years after the Prestige oil spill incident have been reported [8,9]. Performing experiments under controlled environmental conditions may increase our understanding of the effects on people years after the exposure
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