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Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach / SARAH MITCHELL

Swansea University Author: SARAH MITCHELL

  • Version of Record under embargo until: 9th June 2027

DOI (Published version): 10.23889/SUthesis.60181

Abstract

The number of users of e-cigarettes continues to rise, with most people opting to use electronic cigarette devices to help quit smoking tobacco cigarettes. Some non-smokers and young people are also choosing to use the devices, even if they are never-smokers. The increasing number of users of e-ciga...

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Published: Swansea 2022
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Clift, Martin J D. ; Doak, Shareen H. ; Challenger-Williams, Tom
URI: https://cronfa.swan.ac.uk/Record/cronfa60181
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first_indexed 2022-06-13T08:37:01Z
last_indexed 2022-06-14T03:18:49Z
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spelling 2022-06-13T09:51:17.6323237 v2 60181 2022-06-13 Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach 4d1a7f9f5a9624db92e603b9e71dd8e9 SARAH MITCHELL SARAH MITCHELL true false 2022-06-13 The number of users of e-cigarettes continues to rise, with most people opting to use electronic cigarette devices to help quit smoking tobacco cigarettes. Some non-smokers and young people are also choosing to use the devices, even if they are never-smokers. The increasing number of users of e-cigarettes and demographic of users reminds us that conducting relevant research in this area is crucial for many reasons. Although important, a lack of available relevant models to test e-cigarettes has led to a low availability of data to address concerns regarding human health hazards. Here, an in vitro model of the alveolar barrier has been created for use with a vaping machine which can directly expose cell cultures to vapour, collect emitted particles and detect chemical components independently. The model consists of an alveolar type 1-like cell line (TT1), an alveolar type 2-like cell line (NCI-H441) and macrophages (dTHP-1). This multi-cellular system formulates the ability for cells to be cultured at the air-liquid interface (ALI), that mimics the alveolar region of the human lung. Once the in vitro model was fully developed, specific e-cigarette flavour syrups were selected based on their popularity (purchase levels) and the flavours containing (the most hazardous) chemicals of interest. Flavour syrups were then exposed to cell cultures using specific puff profiles to recreate direct human exposure to understand the potential risk to human health by assessing cytotoxicity, oxidative stress, measuring (pro-)inflammatory and (pro-)fibrotic mediators, and genotoxicity. Results showed that TT1, NCI-H441 and dTHP-1 cells can be cultured together in both submerged and ALI conditions. It is proposed that this cell culture model can be successfully used in future to assess potential toxicity of e-cigarette vapours and e-liquids and be used to compare to tobacco cigarette smoke. After exposure to e-liquids and vapours, TT1 cells were most sensitive to nicotine, and overall, flavoured e-liquids and vapours caused the most pronounced effects in triple cell culture and all co-culture types. These findings suggest that e-cigarette liquids and vapours are not without risks to human health, and should be routinely assessed for toxic effects, especially when containing nicotine or flavourings. E-Thesis Swansea Toxicology, In vitro, cell culture, e-cigarette, vaping, co-culture 9 6 2022 2022-06-09 10.23889/SUthesis.60181 COLLEGE NANME COLLEGE CODE Swansea University Clift, Martin J D. ; Doak, Shareen H. ; Challenger-Williams, Tom Doctoral Ph.D part funded by Knowledge Economy Skills Scholarships (KESS) 2022-06-13T09:51:17.6323237 2022-06-13T09:29:26.7427655 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine SARAH MITCHELL 1 Under embargo Under embargo 2022-06-13T09:50:28.0795640 Output 5656654 application/pdf Version of Record true 2027-06-09T00:00:00.0000000 Copyright: The author, Sarah M. Mitchell, 2022. true eng
title Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
spellingShingle Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
SARAH MITCHELL
title_short Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
title_full Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
title_fullStr Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
title_full_unstemmed Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
title_sort Investigating the human health implications of e-cigarettes - An in vitro mechanistic toxicology approach
author_id_str_mv 4d1a7f9f5a9624db92e603b9e71dd8e9
author_id_fullname_str_mv 4d1a7f9f5a9624db92e603b9e71dd8e9_***_SARAH MITCHELL
author SARAH MITCHELL
author2 SARAH MITCHELL
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publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.60181
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description The number of users of e-cigarettes continues to rise, with most people opting to use electronic cigarette devices to help quit smoking tobacco cigarettes. Some non-smokers and young people are also choosing to use the devices, even if they are never-smokers. The increasing number of users of e-cigarettes and demographic of users reminds us that conducting relevant research in this area is crucial for many reasons. Although important, a lack of available relevant models to test e-cigarettes has led to a low availability of data to address concerns regarding human health hazards. Here, an in vitro model of the alveolar barrier has been created for use with a vaping machine which can directly expose cell cultures to vapour, collect emitted particles and detect chemical components independently. The model consists of an alveolar type 1-like cell line (TT1), an alveolar type 2-like cell line (NCI-H441) and macrophages (dTHP-1). This multi-cellular system formulates the ability for cells to be cultured at the air-liquid interface (ALI), that mimics the alveolar region of the human lung. Once the in vitro model was fully developed, specific e-cigarette flavour syrups were selected based on their popularity (purchase levels) and the flavours containing (the most hazardous) chemicals of interest. Flavour syrups were then exposed to cell cultures using specific puff profiles to recreate direct human exposure to understand the potential risk to human health by assessing cytotoxicity, oxidative stress, measuring (pro-)inflammatory and (pro-)fibrotic mediators, and genotoxicity. Results showed that TT1, NCI-H441 and dTHP-1 cells can be cultured together in both submerged and ALI conditions. It is proposed that this cell culture model can be successfully used in future to assess potential toxicity of e-cigarette vapours and e-liquids and be used to compare to tobacco cigarette smoke. After exposure to e-liquids and vapours, TT1 cells were most sensitive to nicotine, and overall, flavoured e-liquids and vapours caused the most pronounced effects in triple cell culture and all co-culture types. These findings suggest that e-cigarette liquids and vapours are not without risks to human health, and should be routinely assessed for toxic effects, especially when containing nicotine or flavourings.
published_date 2022-06-09T04:18:05Z
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