In vitro RNA-seq-based toxicogenomics assessment shows reduced biological effect of tobacco heating products when compared to cigarette smoke

Haswell, Linsey E.; Corke, Sarah; Verrastro, Ivan; Baxter, Andrew; Banerjee, Anisha; Adamson, Jason; Jaunky, Tomasz; Proctor, Christopher; Gaça, Marianna; Minet, Emmanuel

doi:10.1038/s41598-018-19627-0

Cited by 36 publications

(38 citation statements)

References 47 publications

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“…To model cannabis smoke exposure, we used smoke conditioned media methods that have been validated for tobacco combustion experiments (Wirtz and Schmidt, ; Bernhard et al, ; Bauer et al, ; Hudy et al, ; Hudy and Proud, ; Hudy et al, ; Amatngalim et al, ; Jamieson et al, ). Comparison of differential gene expression patterns from our tobacco smoke conditioned media experiments in Calu‐3 cells to bronchial brushings from human tobacco smokers (Harvey et al, ; Tilley et al, ) and air‐liquid interface cultures of primary epithelial cells exposed to mainstream tobacco smoke (Mathis et al, ; Haswell et al, ; Haswell et al, ) revealed overlap, validating the relevance of our model. Using cannabis smoke conditioned media, we observed functional and transcriptional responses that were shared with tobacco smoke.…”

Section: Introductionsupporting

confidence: 67%

“…Smoke conditioned media methods typically filter coarse particulates and extract water‐soluble components of smoke combustion. The reduction in compositional complexity of smoke conditioned media relative to mainstream smoke may be important, although our data and those of others (Mathis et al, ; Haswell et al, ; Haswell et al, ) demonstrate that major transcriptional changes are conserved in either model system (smoke conditioned media or mainstream smoke) and both are reflective of in situ human biology (Harvey et al, ; Tilley et al, ). Importantly, the presence or absence of filters in tobacco (cellulose acetate) and cannabis smoke (cardboard) exposure models should be considered in interpreting the present data and designing future experiments (Aufderheide et al, ).…”

Section: Discussioncontrasting

confidence: 43%

“…A–B). Furthermore, expression levels of differentially expressed genes were also correlated ( r = 0.770, P = 3.0*10 −8 and r = 0.665, P = 1.6*10 ‐12 ) between tobacco smoke exposure Calu‐3 cells and air‐liquid interface cultures of primary human airway epithelial cells exposed to mainstream tobacco smoke in two independent datasets (SRP096285 and SRP126155)(Haswell et al, ; Haswell et al, )(Fig. C–D).…”

Section: Resultsmentioning

confidence: 85%

“…To determine the ability of this model to recapitulate biologically relevant gene expression patterns, we generated an RNA‐sequencing transcriptomic dataset of Calu‐3 cells following 24h tobacco smoke exposure (10% TSE) and compared it with previous transcriptomic datasets derived from (1) airway epithelial cells isolated from bronchial brushings of lifetime tobacco smokers; (2) primary human airway epithelial cells grown under air‐liquid interface culture conditions and acutely exposed to main stream tobacco smoke (Harvey et al, ; Tilley et al, ; Haswell et al, ; Haswell et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…To determine the ability of this model to recapitulate biologically relevant gene expression patterns, we generated an RNA-sequencing transcriptomic dataset of Calu-3 cells following 24h tobacco smoke exposure (10% TSE) and compared it with previous transcriptomic datasets derived from (1) airway epithelial cells isolated from bronchial brushings of lifetime tobacco smokers; (2) primary human airway epithelial cells grown under air-liquid interface culture conditions and acutely exposed to main stream tobacco smoke (Harvey et al, 2007;Tilley et al, 2011;Haswell et al, 2017;Haswell et al, 2018). Correlation of Calu-3 cell differential gene expression profile (log2FoldChange (FC)) following exposure to tobacco smoke extract (TSE) and differential gene expression profiles between healthy controls and lifetime smokers in the publicly available datasets (A) GSE4498 and (B) GSE11784.…”

Section: In Vitro Cannabis Smoke Exposure-induced Changes In Gene Expmentioning

confidence: 99%

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Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke

et al. 2019

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Globally, many jurisdictions are legalizing or decriminalizing cannabis, creating a potential public health issue that would benefit from experimental evidence to inform policy, government regulations, and user practices. Tobacco smoke exposure science has created a body of knowledge that demonstrates the conclusive negative impacts on respiratory health; similar knowledge remains to be established for cannabis. To address this unmet need, we performed in vitro functional and transcriptomic experiments with a human airway epithelial cell line (Calu‐3) exposed to cannabis smoke, with tobacco smoke as a positive control. Demonstrating the validity of our in vitro model, tobacco smoke induced gene expression profiles that were significantly correlated with gene expression profiles from published tobacco exposure datasets from bronchial brushings and primary human airway epithelial cell cultures. Applying our model to cannabis smoke, we demonstrate that cannabis smoke induced functional and transcriptional responses that overlapped with tobacco smoke. Ontology and pathway analysis revealed that cannabis smoke induced DNA replication and oxidative stress responses. Functionally, cannabis smoke impaired epithelial cell barrier function, antiviral responses, and increased inflammatory mediator production. Our study reveals striking similarities between cannabis and tobacco smoke exposure on impairing barrier function, suppressing antiviral pathways, potentiating of pro‐inflammatory mediators, and inducing oncogenic and oxidative stress gene expression signatures. Collectively our data suggest that cannabis smoke exposure is not innocuous and may possess many of the deleterious properties of tobacco smoke, warranting additional studies to support public policy, government regulations, and user practices.

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Section: Introductionsupporting

confidence: 67%

Section: Discussioncontrasting

confidence: 43%

Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: In Vitro Cannabis Smoke Exposure-induced Changes In Gene Expmentioning

confidence: 99%

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Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke

et al. 2019

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Assessing the lung cancer risk reduction potential of candidate modified risk tobacco products

et al. 2019

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Smoking is the major cause of lung cancer. While the risk of lung cancer increases with the number of cigarettes smoked and the duration of smoking, it also decreases upon smoking cessation. The development of candidate modified risk tobacco products (cMRTP) is aimed at providing smokers who will not quit with alternatives to cigarettes that present less risk of harm and smoking-related disease. It is necessary to assess the risk reduction potential of cMRTPs, including their potential to reduce the risk of lung cancer. Assessing the lung cancer risk reduction potential of cMRTPs is hampered by (i) the absence of clinical risk markers that are predictive of future lung cancer development, (ii) the latency of lung cancer manifestation (decades of smoking), and (iii) the slow reduction in excess risk upon cessation and a fortiori upon switching to a cMRTP. It is, therefore, likely that only long-term epidemiology will provide definitive answers to this question and allow to first verify that a cMRTP reduces the risk of lung cancer and if it does, to quantify the reduction in excess lung cancer risk associated with a cMRTP. For this to be possible, the cMRTP would need to be available in the market and used exclusively by a large portion of current smokers. Here, we propose that a mechanism-based approach represents a solid alternative to show in a pre-market setting that switching to a cMRTP is likely to significantly reduce the risk of lung cancer. This approach is based on the causal chain of events that leads from smoking to disease and leverages both non-clinical and clinical studies as well as the principles of systems toxicology. We also discuss several important challenges inherent to the assessment of cMRTPs as well as key aspects regarding product use behavior.

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Changes in biomarkers of exposure and biomarkers of potential harm after 360 days in smokers who either continue to smoke, switch to a tobacco heating product or quit smoking

Gale¹,

McEwan²,

Hardie³

et al. 2022

Intern Emerg Med

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The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers either continue to smoke or switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting over the period of a year, and to compare any changes with smokers who quit tobacco use completely and with never smokers’ biomarker levels. Participants in this year-long ambulatory study were healthy smokers with a self-reported low intent to quit assigned either to continue smoking or switch to a THP; a group of smokers with a self-reported high intent to quit who abstained from tobacco use; and a group of never smokers. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases and cancer were assessed at baseline and up to 360 days. Substantial and sustained reductions in BoE levels were found at 360 days for both participants who switched from smoking to THP use and participants who quit smoking, in many cases the reductions being of a similar order for both groups. The never smoker group typically had lower levels of the measured BoEs than either of these groups, and much lower levels than participants who continued to smoke. Several BoPHs were found to change in a favourable direction (towards never smoker levels) over the year study for participants who completely switched to THP or quit, while BoPHs such as soluble intercellular adhesion molecule-1 were found to change in an unfavourable direction (away from never smoker levels) in participants who continued to smoke. Our findings, alongside chemical and toxicological studies undertaken on the THP used in this study, lead to the conclusion that smokers who would have otherwise continued to smoke and instead switch entirely to the use of this THP, will reduce their exposure to tobacco smoke toxicants and as a consequence are reasonably likely to reduce disease risks compared to those continuing to smoke.

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In vitro RNA-seq-based toxicogenomics assessment shows reduced biological effect of tobacco heating products when compared to cigarette smoke

Cited by 36 publications

References 47 publications

Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke

Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke

Assessing the lung cancer risk reduction potential of candidate modified risk tobacco products

Changes in biomarkers of exposure and biomarkers of potential harm after 360 days in smokers who either continue to smoke, switch to a tobacco heating product or quit smoking

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