Effects of corexit oil dispersants and the WAF of dispersed oil on DNA damage and repair in cultured human bronchial airway cells, BEAS-2B

Major, Danielle; Derbes, Rebecca S.; Wang, He; Roy-Engel, Astrid M.

doi:10.1016/j.genrep.2015.12.002

Cited by 8 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our initial experiment with three female mice was designed to determine a dose of Corexit 9500+oil SAF that caused lung injury in mice. Previous experiments indicated that the Corexit 9500+oil and Corexit 9527+oil SAF displayed similar toxicity curves with BEAS-2B cells in culture and that at 1/100 dilution of both solutions was toxic [ 27 ]. Therefore, mice were treated by oropharyngeal aspiration with 50µL of the 1/100 dilution SAF and 10-fold higher (1/10) and lower dilutions (1/1,000) SAF to assess their tolerability.…”

Section: Resultsmentioning

confidence: 99%

The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses

Liu

Miller

Zhuang

et al. 2020

IJERPH

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses

Liu

Miller

Zhuang

et al. 2020

IJERPH

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown an association between exposure to crude oil and adverse effects among spill responders ( Aguilera et al 2010 ; Laffon et al 2016 ), but no previous spill involved this level of dispersant use or resulted in an investigation of potential associations between dispersant use and adverse health effects. In vitro results suggested that 9527A and 9500A may have adverse effects on human lung tissue ( Major et al 2016 ; Shi et al 2013 ). Our results provide epidemiological evidence to suggest that exposure to 9527A or 9500A may be associated with adverse health effects, even after taking into account exposure to the crude oil.…”

Section: Discussionmentioning

confidence: 99%

“…Using in vitro cultures of human bronchial cells, Shi et al ( 2013 ) showed that exposure to either 9500A or 9527A resulted in a significant loss of cell viability and that the loss of viability was dose-dependent. Similarly, Major et al ( 2016 ) found that exposing human bronchial cells to individual mixtures of 9500A and 9527A with crude oil induced both cytotoxic and genotoxic effects. Although data on toxicity of dispersants are limited, there is some evidence of effects caused by the component ingredients of each dispersant.…”

Section: Introductionmentioning

confidence: 90%

Respiratory, Dermal, and Eye Irritation Symptoms Associated with Corexit™ EC9527A/EC9500A following the Deepwater Horizon Oil Spill: Findings from the GuLF STUDY

McGowan

Kwok

Engel

et al. 2017

Environ Health Perspect

View full text Add to dashboard Cite

Background:The large quantities of chemical oil dispersants used in the oil spill response and cleanup (OSRC) work following the Deepwater Horizon disaster provide an opportunity to study associations between dispersant exposure (Corexit™ EC9500A or EC9527A) and human health.Objectives:Our objectives were to examine associations between potential exposure to the dispersants and adverse respiratory, dermal, and eye irritation symptoms.Methods:Using data from detailed Gulf Long-term Follow-up ( GuLF) Study enrollment interviews, we determined potential exposure to either dispersant from participant-reported tasks during the OSRC work. Between 27,659 and 29,468 participants provided information on respiratory, dermal, and eye irritation health. We estimated prevalence ratios (PRs) to measure associations with symptoms reported during the OSRC work and at study enrollment, adjusting for potential confounders including airborne total hydrocarbons exposure, use of cleaning chemicals, and participant demographics.Results:Potential exposure to either of the dispersants was significantly associated with all health outcomes at the time of the OSRC, with the strongest association for burning in the nose, throat, or lungs [adjusted PR (aPR)=1.61 (95% CI: 1.42, 1.82)], tightness in chest [aPR=1.58 (95% CI: 1.37, 1.81)], and burning eyes [aPR=1.48 (95% CI: 1.35, 1.64). Weaker, but still significant, associations were found between dispersant exposure and symptoms present at enrollment.Conclusions:Potential exposure to Corexit™ EC9527A or EC9500A was associated with a range of health symptoms at the time of the OSRC, as well as at the time of study enrollment, 1–3 y after the spill. https://doi.org/10.1289/EHP1677

show abstract

“…The neutral comet assay, a standard and sensitive technique to analyse DNA DSBs, was used in BEP2D cells. 36 BEP2D cells were treated with exosomes following 2 Gy irradiation and transfected with 50 and 100 nM miR-1246 mimic or mimic-NC for 24 h, respectively. Then, cells were trypsinised and resuspended in 1× PBS to a final concentration of 1×10 4 cells/mL.…”

Section: Methodsmentioning

confidence: 99%

Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4

Song

Huang

et al. 2018

Br J Cancer

View full text Add to dashboard Cite

Background An increasing number of studies have recently reported that microRNAs packaged in exosomes contribute to multiple biological processes such as cancer progression; however, little is known about their role in the development of radiation-induced bystander effects. Methods The exosomes were isolated from the culture medium of BEP2D cells with or without γ-ray irradiation by ultracentrifugation. To monitor DNA damage and repair efficiency, the DNA double-strand break biomarker 53BP1 foci, comet, micronuclei, expression of DNA repair genes and NHEJ repair activity were detected. The miR-1246 targeting sequence of the DNA ligase 4 ( LIG4 ) mRNA 3′UTR was assessed by luciferase reporter vectors. Results miR-1246 was increased in exosomes secreted from 2 Gy-irradiated BEP2D cells and inhibited the proliferation of nonirradiated cells. The miR-1246 mimic, exosomes from irradiated cells, and radiation-conditioned cell culture medium increased the yields of 53BP1 foci, comet tail and micronuclei in nonirradiated cells, and decreased NHEJ efficiency. miR-1246 downregulated LIG4 expression by directly targeting its 3′UTR. Conclusions Our findings demonstrate that miR-1246 packaged in exosomes could act as a transfer messenger and contribute to DNA damage by directly repressing the LIG4 gene. Exosomal miR-1246 may be a critical predictor of and player in radiation-induced bystander DNA damage.

show abstract

Effects of corexit oil dispersants and the WAF of dispersed oil on DNA damage and repair in cultured human bronchial airway cells, BEAS-2B

Cited by 8 publications

References 34 publications

The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses

The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses

Respiratory, Dermal, and Eye Irritation Symptoms Associated with Corexit™ EC9527A/EC9500A following the Deepwater Horizon Oil Spill: Findings from the GuLF STUDY

Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4

Contact Info

Product

Resources

About