API XML

This AOP is licensed under the BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

AOP: 409

Title

A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.  More help

Frustrated phagocytosis leads to malignant mesothelioma

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
Frustrated phagocytosis leads to malignant mesothelioma
The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter. More help
Handbook Version v2.0

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help
Click to download graphical representation template Explore AOP in a Third Party Tool

Authors

The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Nureddin K. Mansour, Università degli Studi, Milan, Italy

Merlin Mei, Environmental Protection Agency, US

Marvin Martens, Maastricht University, Netherlands

Franziska Kreidl, Maastricht University, Netherlands

Holly Mortensen, Environmental Protection Agency, US

Penny Nymark, Insititute of Environmental Medicine, Karolinska Insitutet, Sweden

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.   More help
Evgeniia Kazymova   (email point of contact)

Contributors

Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • Nureddin Mansour
  • Penny Nymark
  • Merlin Mei
  • Evgeniia Kazymova

Coaches

This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author. More help

OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication.   More help
OECD Project # OECD Status Reviewer's Reports Journal-format Article OECD iLibrary Published Version
This AOP was last modified on May 26, 2024 20:39

Revision dates for related pages

Page Revision Date/Time
Frustrated phagocytosis September 16, 2022 09:03
Increased, secretion of proinflammatory mediators May 17, 2023 15:18
Increased, recruitment of inflammatory cells May 12, 2023 17:03
Increased, Reactive oxygen species April 10, 2024 17:33
Increased, DNA damage and mutation August 13, 2019 05:41
Genomic instability July 06, 2021 06:05
Increase, Cell Proliferation March 08, 2024 12:25
Increased, mesotheliomas December 03, 2016 16:37
Frustrated phagocytosis leads to Increased proinflammatory mediators July 06, 2021 06:10
Frustrated phagocytosis leads to Increased, Reactive oxygen species July 06, 2021 06:11
Increased proinflammatory mediators leads to Recruitment of inflammatory cells May 18, 2023 12:46
Recruitment of inflammatory cells leads to Increased, Reactive oxygen species July 03, 2019 11:53
Increased, Reactive oxygen species leads to Increased, DNA damage and mutation July 03, 2019 11:53
Increased, DNA damage and mutation leads to Genomic instability July 06, 2021 06:12
Genomic instability leads to Increase, Cell Proliferation July 06, 2021 06:12
Increase, Cell Proliferation leads to Increased, mesotheliomas July 06, 2021 06:13
Multi-walled carbon nanotubes July 26, 2017 18:59
Asbestos fibers September 02, 2021 09:31
High aspect ratio material August 13, 2019 04:38
Carbon nanotubes August 09, 2017 08:03
Carbon nanotubes, Multi-walled carbon nanotubes, single-walled carbon nanotubes, carbon nanofibres January 01, 2018 17:52
Single walled carbon nanotubes July 26, 2017 18:58

Abstract

A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

This AOP starts with frustrated phagocytosis, meaning that macrophages fail to engulf long fibers and die with a concomitant massive release of ROS and pro-inflammatory signals. Any fibre that exceeds a maximum length for macrophage uptake will result in frustrated phagocytosis. The release of ROS and pro-inflammatory signals together with persistent cytotoxicity and tissue injury in the pleura can lead to secondary genotoxicity, including oxidative lesions to DNA. When DNA repair pathways are overwhelmed and the DNA lesions exceed the repair capacity, it may lead to mutagenesis with increased mutations and DNA double strand breaks. Increased DNA damage increases the risk for genomic instability and accumulation of mutations in mesothelial cells. Specific mutations and chromosomal aberrations have been associated with mesothelioma, including for example mutation of BAP1 and other genes, and  loss of chromosomal regions 3p21 (which harbours the BAP1 gene) and 9p21. These mutations and deletions are assumed to be involved in the molecular and genetic alterations that drive mesothelial cell proliferation, which is the final key event leading to the adverse outcome: malignant pleural mesothelioma.

There is abundant evidence for this process taking place in humans exposed to asbestos fibres. Recently, experimental evidence from both in vivo and in vitro studies indicate that a similar process may take place in humans exposed to cetrain types of nanomaterials with high aspect ratios, such as multi-walled carbon nanotubes.

AOP Development Strategy

Context

Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Strategy

Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components.  Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Summary of the AOP

This section is for information that describes the overall AOP.The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help

Events:

Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help
Key Events (KE)
A measurable event within a specific biological level of organisation. More help
Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help
Type Event ID Title Short name
MIE 1668 Frustrated phagocytosis Frustrated phagocytosis
KE 1496 Increased, secretion of proinflammatory mediators Increased proinflammatory mediators
KE 1497 Increased, recruitment of inflammatory cells Recruitment of inflammatory cells
KE 1115 Increased, Reactive oxygen species Increased, Reactive oxygen species
KE 1669 Increased, DNA damage and mutation Increased, DNA damage and mutation
KE 1896 Genomic instability Genomic instability
KE 870 Increase, Cell Proliferation Increase, Cell Proliferation
AO 1090 Increased, mesotheliomas Increased, mesotheliomas

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help
Title Adjacency Evidence Quantitative Understanding
Frustrated phagocytosis leads to Increased proinflammatory mediators adjacent High Not Specified
Increased proinflammatory mediators leads to Recruitment of inflammatory cells adjacent High Not Specified
Recruitment of inflammatory cells leads to Increased, Reactive oxygen species adjacent High Not Specified
Increased, Reactive oxygen species leads to Increased, DNA damage and mutation adjacent High Not Specified
Increased, DNA damage and mutation leads to Genomic instability adjacent High Not Specified
Genomic instability leads to Increase, Cell Proliferation adjacent Not Specified Not Specified
Increase, Cell Proliferation leads to Increased, mesotheliomas adjacent High Not Specified
Frustrated phagocytosis leads to Increased, Reactive oxygen species non-adjacent High Not Specified

Network View

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help
Name
Multi-walled carbon nanotubes
Asbestos fibers
High aspect ratio material
Carbon nanotubes
Carbon nanotubes, Multi-walled carbon nanotubes, single-walled carbon nanotubes, carbon nanofibres
Single walled carbon nanotubes

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available. More help

Sex Applicability

The sex for which the AOP is known to be applicable. More help

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help
Modulating Factor (MF) Influence or Outcome KER(s) involved
     

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors.  More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

References

List of the literature that was cited for this AOP. More help
  1. Affar, El Bachir, and Michele Carbone. ‘BAP1 Regulates Different Mechanisms of Cell Death’. Cell Death & Disease 9, no. 12 (December 2018): 1151. https://doi.org/10.1038/s41419-018-1206-5.
  2. Betti, Marta, Elisabetta Casalone, Daniela Ferrante, Anna Aspesi, Giulia Morleo, Alessandra Biasi, Marika Sculco, et al. ‘Germline Mutations in DNA Repair Genes Predispose Asbestos-Exposed Patients to Malignant Pleural Mesothelioma’. Cancer Letters 405 (1 October 2017): 38–45. https://doi.org/10.1016/j.canlet.2017.06.028.
  3. Bott, Matthew, Marie Brevet, Barry S Taylor, Shigeki Shimizu, Tatsuo Ito, Lu Wang, Jenette Creaney, et al. ‘The Nuclear Deubiquitinase BAP1 Is Commonly Inactivated by Somatic Mutations and 3p21.1 Losses in Malignant Pleural Mesothelioma’. Nature Genetics 43, no. 7 (July 2011): 668–72. https://doi.org/10.1038/ng.855.
  4. Boyles, Matthew S. P., Lesley Young, David M. Brown, Laura MacCalman, Hilary Cowie, Anna Moisala, Fiona Smail, et al. ‘Multi-Walled Carbon Nanotube Induced Frustrated Phagocytosis, Cytotoxicity and pro-Inflammatory Conditions in Macrophages Are Length Dependent and Greater than That of Asbestos’. Toxicology in Vitro 29, no. 7 (1 October 2015): 1513–28. https://doi.org/10.1016/j.tiv.2015.06.012.
  5. Bryant, P.E. ‘Enzymatic Restriction of Mammalian Cell DNA Using Pvu II and Bam H1: Evidence for the Double-Strand Break Origin of Chromosomal Aberrations’. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine 46, no. 1 (January 1984): 57–65. https://doi.org/10.1080/09553008414551061.
  6. Chernova, Tatyana. ‘Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf)’, n.d., 20.
  7. Chew, Shan Hwu, and Shinya Toyokuni. ‘Malignant Mesothelioma as an Oxidative Stress-Induced Cancer: An Update’. Free Radical Biology and Medicine 86 (1 September 2015): 166–78. https://doi.org/10.1016/j.freeradbiomed.2015.05.002.
  8. Donaldson, Ken, Fiona A. Murphy, Rodger Duffin, and Craig A. Poland. ‘Asbestos, Carbon Nanotubes and the Pleural Mesothelium: A Review of the Hypothesis Regarding the Role of Long Fibre Retention in the Parietal Pleura, Inflammation and Mesothelioma’. Particle and Fibre Toxicology 7, no. 1 (22 March 2010): 5. https://doi.org/10.1186/1743-8977-7-5.
  9. Emerce, Esra, Manosij Ghosh, Deniz Öner, Radu-Corneliu Duca, Jeroen Vanoirbeek, Bram Bekaert, Peter H. M. Hoet, and Lode Godderis. ‘Carbon Nanotube- and Asbestos-Induced DNA and RNA Methylation Changes in Bronchial Epithelial Cells’. Chemical Research in Toxicology, 23 April 2019, acs.chemrestox.8b00406. https://doi.org/10.1021/acs.chemrestox.8b00406.
  10. Feldmann, E., V. Schmiemann, W. Goedecke, S. Reichenberger, and P. Pfeiffer. ‘DNA Double-Strand Break Repair in Cell-Free Extracts from Ku80-Deficient Cells: Implications for Ku Serving as an Alignment Factor in Non-Homologous DNA End Joining’. Nucleic Acids Research 28, no. 13 (1 July 2000): 2585–96. https://doi.org/10.1093/nar/28.13.2585.
  11. Godleski, John J. ‘Role of Asbestos in Etiology of Malignant Pleural Mesothelioma’. Thoracic Surgery Clinics 14, no. 4 (November 2004): 479–87. https://doi.org/10.1016/S1547-4127(04)00111-2.
  12. Hylebos, Marieke, Guy Van Camp, Jan P van Meerbeeck, and Ken Op de Beeck. ‘The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing’. Journal of Thoracic Oncology 11, no. 10 (1 October 2016): 1615–26. https://doi.org/10.1016/j.jtho.2016.05.020.
  13. Kim, Jeong Eun, Deokhoon Kim, Yong Sang Hong, Kyu-pyo Kim, Young Kwang Yoon, Dae Ho Lee, Sang-We Kim, Sung-Min Chun, Se Jin Jang, and Tae Won Kim. ‘Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS’. Translational Oncology 11, no. 2 (1 April 2018): 268–74. https://doi.org/10.1016/j.tranon.2018.01.005.
  14. Kolb, Thorsten, and Aurélie Ernst. ‘Cell-Based Model Systems for Genome Instability: Dissecting the Mechanistic Basis of Chromothripsis in Cancer’. International Journal of Cancer n/a, no. n/a. Accessed 22 June 2021. https://doi.org/10.1002/ijc.33618.
  15. Lindberg, Hanna K., Ghita C. -M. Falck, Rajinder Singh, Satu Suhonen, Hilkka Järventaus, Esa Vanhala, Julia Catalán, Peter B. Farmer, Kai M. Savolainen, and Hannu Norppa. ‘Genotoxicity of Short Single-Wall and Multi-Wall Carbon Nanotubes in Human Bronchial Epithelial and Mesothelial Cells in Vitro’. Toxicology, Nanotoxicology, 313, no. 1 (8 November 2013): 24–37. https://doi.org/10.1016/j.tox.2012.12.008.
  16. Malkin, D, F. Li, L. Strong, J. Fraumeni, C. Nelson, D. Kim, J Kassel, et al. ‘Germ Line P53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms’. Science 250, no. 4985 (30 November 1990): 1233–38. https://doi.org/10.1126/science.1978757.
  17. Mansfield, Aaron S., Tobias Peikert, James B. Smadbeck, Julia B. M. Udell, Enrique Garcia-Rivera, Laura Elsbernd, Courtney L. Erskine, et al. ‘Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma’. Journal of Thoracic Oncology 14, no. 2 (1 February 2019): 276–87. https://doi.org/10.1016/j.jtho.2018.10.001.
  18. Matsumoto, Shinji, Kazuki Nabeshima, Makoto Hamasaki, Tatsuki Shibuta, and Tsukuru Umemura. ‘Upregulation of MicroRNA-31 Associates with a Poor Prognosis of Malignant Pleural Mesothelioma with Sarcomatoid Component’. Medical Oncology 31, no. 12 (December 2014): 303. https://doi.org/10.1007/s12032-014-0303-2.
  19. McMahon, Stephen J., Jan Schuemann, Harald Paganetti, and Kevin M. Prise. ‘Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage’. Scientific Reports 6, no. 1 (December 2016): 33290. https://doi.org/10.1038/srep33290.
  20. Møller, Peter, and Nicklas Raun Jacobsen. ‘Weight of Evidence Analysis for Assessing the Genotoxic Potential of Carbon Nanotubes’. Critical Reviews in Toxicology 47, no. 10 (26 November 2017): 871–88. https://doi.org/10.1080/10408444.2017.1367755.
  21. Morimoto, Yasuo, Hiroto Izumi, and Etsushi Kuroda. ‘Significance of Persistent Inflammation in Respiratory Disorders Induced by Nanoparticles’. Journal of Immunology Research 2014 (2014): 1–8. https://doi.org/10.1155/2014/962871.
  22. Murali, Rajmohan, Thomas Wiesner, and Richard A. Scolyer. ‘Tumours Associated with BAP1 Mutations’. Pathology 45, no. 2 (1 February 2013): 116–26. https://doi.org/10.1097/PAT.0b013e32835d0efb.
  23. Murphy, Fiona A., Anja Schinwald, Craig A. Poland, and Ken Donaldson. ‘The Mechanism of Pleural Inflammation by Long Carbon Nanotubes: Interaction of Long Fibres with Macrophages Stimulates Them to Amplify pro-Inflammatory Responses in Mesothelial Cells’. Particle and Fibre Toxicology 9, no. 1 (3 April 2012): 8. https://doi.org/10.1186/1743-8977-9-8.
  24. Nagai, Hirotaka, and Shinya Toyokuni. ‘Biopersistent Fiber-Induced Inflammation and Carcinogenesis: Lessons Learned from Asbestos toward Safety of Fibrous Nanomaterials’. Archives of Biochemistry and Biophysics 502, no. 1 (1 October 2010): 1–7. https://doi.org/10.1016/j.abb.2010.06.015.
  25. Nasu, Masaki, Mitsuru Emi, Sandra Pastorino, Mika Tanji, Amy Powers, Hugh Luk, Francine Baumann, et al. ‘High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma’. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 10, no. 4 (April 2015): 565–76. https://doi.org/10.1097/JTO.0000000000000471.
  26. Natarajan, A.T., F. Darroudi, L.H.F. Mullenders, and M. Meijers. ‘The Nature and Repair of DNA Lesions That Lead to Chromosomal Aberrations Induced by Ionizing Radiations’. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 160, no. 3 (May 1986): 231–36. https://doi.org/10.1016/0027-5107(86)90132-6.
  27. Nymark, Penny, Pekka Kohonen, Vesa Hongisto, and Roland C. Grafström. ‘Toxic and Genomic Influences of Inhaled Nanomaterials as a Basis for Predicting Adverse Outcome’. Annals of the American Thoracic Society 15, no. Supplement_2 (April 2018): S91–97. https://doi.org/10.1513/AnnalsATS.201706-478MG.
  28. Nymark, Penny, Harriet Wikman, Tuija Hienonen-Kempas, and Sisko Anttila. ‘Molecular and Genetic Changes in Asbestos-Related Lung Cancer’. Cancer Letters 265, no. 1 (28 June 2008): 1–15. https://doi.org/10.1016/j.canlet.2008.02.043.
  29. Oey, Harald, Marissa Daniels, Vandana Relan, Tian Mun Chee, Morgan R Davidson, Ian A Yang, Jonathan J Ellis, Kwun M Fong, Lutz Krause, and Rayleen V Bowman. ‘Whole-Genome Sequencing of Human Malignant Mesothelioma Tumours and Cell Lines’. Carcinogenesis 40, no. 6 (6 July 2019): 724–34. https://doi.org/10.1093/carcin/bgz066.
  30. Pass, Harvey I., Chandra Goparaju, Sergey Ivanov, Jessica Donington, Michele Carbone, Moshe Hoshen, Dalia Cohen, et al. ‘Hsa-Mir-29c* Is Linked to the Prognosis of Malignant Pleural Mesothelioma’. Cancer Research 70, no. 5 (1 March 2010): 1916–24. https://doi.org/10.1158/0008-5472.CAN-09-3993.
  31. Pociask, Derek A, Patricia J Sime, and Arnold R Brody. ‘Asbestos-Derived Reactive Oxygen Species Activate TGF-Β1’. Laboratory Investigation 84, no. 8 (August 2004): 1013–23. https://doi.org/10.1038/labinvest.3700109.
  32. Przybytkowski, Ewa, Elizabeth Lenkiewicz, Michael T Barrett, Kathleen Klein, Sheida Nabavi, Celia MT Greenwood, and Mark Basik. ‘Chromosome-Breakage Genomic Instability and Chromothripsis in Breast Cancer’. BMC Genomics 15, no. 1 (2014): 579. https://doi.org/10.1186/1471-2164-15-579.
  33. Schinwald, Anja, and Ken Donaldson. ‘Use of Back-Scatter Electron Signals to Visualise Cell/Nanowires Interactions in Vitro and in Vivo; Frustrated Phagocytosis of Long Fibres in Macrophages and Compartmentalisation in Mesothelial Cells in Vivo’, 2012, 14.
  34. ‘Use of Back-Scatter Electron Signals to Visualise Cell/Nanowires Interactions in Vitro and in Vivo; Frustrated Phagocytosis of Long Fibres in Macrophages and Compartmentalisation in Mesothelial Cells in Vivo’. Particle and Fibre Toxicology 9, no. 1 (28 August 2012): 34. https://doi.org/10.1186/1743-8977-9-34.
  35. Siegrist, Katelyn J., Steven H. Reynolds, Dale W. Porter, Robert R. Mercer, Alison K. Bauer, David Lowry, Lorenzo Cena, et al. ‘Mitsui-7, Heat-Treated, and Nitrogen-Doped Multi-Walled Carbon Nanotubes Elicit Genotoxicity in Human Lung Epithelial Cells’. Particle and Fibre Toxicology 16 (7 October 2019). https://doi.org/10.1186/s12989-019-0318-0.
  36. Sishc, Brock J., and Anthony J. Davis. ‘The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer’. Cancers 9, no. 7 (July 2017): 81. https://doi.org/10.3390/cancers9070081.
  37. Smith, J. ‘Impact of DNA Ligase IV on the Fidelity of End Joining in Human Cells’. Nucleic Acids Research 31, no. 8 (15 April 2003): 2157–67. https://doi.org/10.1093/nar/gkg317.
  38. Snyder, Ryan J., Kirsten C. Verhein, Heather L. Vellers, Adam B. Burkholder, Stavros Garantziotis, and Steven R. Kleeberger. ‘Multi-Walled Carbon Nanotubes Upregulate Mitochondrial Gene Expression and Trigger Mitochondrial Dysfunction in Primary Human Bronchial Epithelial Cells’. Nanotoxicology 13, no. 10 (26 November 2019): 1344–61. https://doi.org/10.1080/17435390.2019.1655107.
  39. Stella, Giulia M. ‘Carbon Nanotubes and Pleural Damage: Perspectives of Nanosafety in the Light of Asbestos Experience’. Biointerphases 6, no. 2 (June 2011): P1–17. https://doi.org/10.1116/1.3582324.
  40. Streich, Lukas, Madina Sukhanova, Xinyan Lu, Yi-Hua Chen, Girish Venkataraman, Stephanie Mathews, Shanxiang Zhang, et al. ‘Aggressive Morphologic Variants of Mantle Cell Lymphoma Characterized with High Genomic Instability Showing Frequent Chromothripsis, CDKN2A/B Loss, and TP53 Mutations: A Multi-Institutional Study’. Genes, Chromosomes and Cancer 59, no. 8 (2020): 484–94. https://doi.org/10.1002/gcc.22849.
  41. Takagi, Atsuya, Akihiko Hirose, Mitsuru Futakuchi, Hiroyuki Tsuda, and Jun Kanno. ‘Dose-Dependent Mesothelioma Induction by Intraperitoneal Administration of Multi-Wall Carbon Nanotubes in P53 Heterozygous Mice’. Cancer Science 103, no. 8 (2012): 1440–44. https://doi.org/10.1111/j.1349-7006.2012.02318.x.
  42. Testa, Joseph R., and Anton Berns. ‘Preclinical Models of Malignant Mesothelioma’. Frontiers in Oncology 10 (11 February 2020). https://doi.org/10.3389/fonc.2020.00101.
  43. Toumpanakis, Dimitrios, and Stamatios E. Theocharis. ‘DNA Repair Systems in Malignant Mesothelioma’. Cancer Letters 312, no. 2 (December 2011): 143–49. https://doi.org/10.1016/j.canlet.2011.08.021.
  44. Toyokuni, Shinya. ‘Genotoxicity and Carcinogenicity Risk of Carbon Nanotubes’. Advanced Drug Delivery Reviews, Carbon Nanotubes in Medicine and Biology: Therapy and Diagnostics & Safety and Toxicology, 65, no. 15 (1 December 2013): 2098–2110. https://doi.org/10.1016/j.addr.2013.05.011.
  45. Urso, Loredana, Ilaria Cavallari, Evgeniya Sharova, Francesco Ciccarese, Giulia Pasello, and Vincenzo Ciminale. ‘Metabolic Rewiring and Redox Alterations in Malignant Pleural Mesothelioma’. British Journal of Cancer 122, no. 1 (7 January 2020): 52–61. https://doi.org/10.1038/s41416-019-0661-9.
  46. Wiesner, Thomas, Anna C Obenauf, Rajmohan Murali, Isabella Fried, Klaus G Griewank, Peter Ulz, Christian Windpassinger, et al. ‘Germline Mutations in BAP1 Predispose to Melanocytic Tumors’. Nature Genetics 43, no. 10 (October 2011): 1018–21. https://doi.org/10.1038/ng.910.
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