Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions

Maikawa, Caitlin L.; Zimmerman, Naomi; Rais, Khaled; Shah, Mittal; Hawley, Brie; Pant, Pallavi; Jeong, Cheol–Heon; Delgado-Saborit, Juana María; Volckens, John; Evans, Greg J.; Wallace, James S.; Pollitt, Krystal J. Godri

doi:10.1016/j.scitotenv.2016.06.173

Cited by 25 publications

(14 citation statements)

References 51 publications

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“…A common mechanism of action that PAH and PAH-containing mixtures have been associated with is cellular oxidative stress response, which can cause damage to both DNA and proteins [47,49,90]. Activation of the Ahr has also been linked to oxidative stress responses [91].…”

Section: Resultsmentioning

confidence: 99%

Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard

Shankar

Geier

Truong

et al. 2019

IJMS

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Polycyclic Aromatic Hydrocarbons (PAHs) are diverse environmental pollutants associated with adverse human health effects. Many studies focus on the carcinogenic effects of a limited number of PAHs and there is an increasing need to understand mechanisms of developmental toxicity of more varied yet environmentally relevant PAHs. A previous study characterized the developmental toxicity of 123 PAHs in zebrafish. Based on phenotypic responses ranging from complete inactivity to acute mortality, we classified these PAHs into eight bins, selected 16 representative PAHs, and exposed developing zebrafish to the concentration of each PAH that induced 80% phenotypic effect. We conducted RNA sequencing at 48 h post fertilization to identify gene expression changes as a result of PAH exposure. Using the Context Likelihood of Relatedness algorithm, we inferred a network that links the PAHs based on coordinated gene responses to PAH exposure. The 16 PAHs formed two broad clusters: Cluster A was transcriptionally more similar to the controls, while Cluster B consisted of PAHs that were generally more developmentally toxic, significantly elevated cyp1a transcript levels, and induced Ahr2-dependent Cyp1a protein expression in the skin confirmed by gene-silencing studies. We found that cyp1a transcript levels were associated with transcriptomic response, but not with PAH developmental toxicity. While all cluster B PAHs predominantly activated Ahr2, they also each enriched unique pathways like ion transport signaling, which likely points to differing molecular events between the PAHs downstream of Ahr2. Thus, using a systems biology approach, we have begun to evaluate, classify, and define mechanisms of PAH toxicity.

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Section: Resultsmentioning

confidence: 99%

Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard

Shankar

Geier

Truong

et al. 2019

IJMS

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“…The authors concluded that exposure to gasoline exhaust results in vascular remodeling, as well as increased expression of markers of oxidative stress, which may contribute to the progression of atherosclerosis. A recent study showed that exposure to GDI exhaust contributes to upregulation of genes related to the metabolism of polycyclic aromatic hydrocarbons (PAHs) and oxidative stress (Maikawa et al, 2016). There is significant body of evidence documenting that insoluble particulate matter can initiate inflammatory cascades in lung tissues with resulting morbidity, including carcinogenesis and endothelial dysfunction (Freire et al, 2013;Tamagawa et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Physical, chemical, and toxicological characteristics of particulate emissions from current technology gasoline direct injection vehicles

Yang

Roth

Ruehl

et al. 2019

Science of The Total Environment

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• Cold-start dominated the production of black carbon and particle number emissions. • Elevated PM emissions during the hard accelerations of the test cycle • Overall, GDI PM samples showed that acute exposure toxicity was low for ROS generation and inflammatory potential. • Correlation of trace metals and oxidative potential suggests a role for insoluble particles in inducing oxidative stress.

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“…This dilution factor was selected to align exposures with levels of traffic-related air pollutant that are representative of concentrations measured in Toronto, Canada [ 31 ]. The characteristics of the GDI and f-GDI engine exhaust used for animal exposure in this study have been previously described [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Individual concentrations of PAHs characterized have been previously reported [ 32 ]. High molecular weight PAH species were primarily in the particulate phase, and low molecular weight species were found in the gas phase.…”

Section: Resultsmentioning

confidence: 99%

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Comparison of Airway Responses Induced in a Mouse Model by the Gas and Particulate Fractions of Gasoline Direct Injection Engine Exhaust

Maikawa

Zimmerman

Ramos

et al. 2018

IJERPH

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Diesel exhaust has been associated with asthma, but its response to other engine emissions is not clear. The increasing prevalence of vehicles with gasoline direct injection (GDI) engines motivated this study, and the objective was to evaluate pulmonary responses induced by acute exposure to GDI engine exhaust in an allergic asthma murine model. Mice were sensitized with an allergen to induce airway hyperresponsiveness or treated with saline (non-allergic group). Animals were challenged for 2-h to exhaust from a laboratory GDI engine operated at conditions equivalent to a highway cruise. Exhaust was filtered to assess responses induced by the particulate and gas fractions. Short-term exposure to particulate matter from GDI engine exhaust induced upregulation of genes related to polycyclic aromatic hydrocarbon (PAH) metabolism (Cyp1b1) and inflammation (TNFα) in the lungs of non-allergic mice. High molecular weight PAHs dominated the particulate fraction of the exhaust, and this response was therefore likely attributable to the presence of these PAHs. The particle fraction of GDI engine exhaust further contributed to enhanced methacholine responsiveness in the central and peripheral tissues in animals with airway hyperresponsiveness. As GDI engines gain prevalence in the vehicle fleet, understanding the health impacts of their emissions becomes increasingly important.

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Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions

Cited by 25 publications

References 51 publications

Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard

Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard

Physical, chemical, and toxicological characteristics of particulate emissions from current technology gasoline direct injection vehicles

Comparison of Airway Responses Induced in a Mouse Model by the Gas and Particulate Fractions of Gasoline Direct Injection Engine Exhaust

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