This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Frustrated phagocytosis leads to malignant mesothelioma
Point of Contact
- Nureddin Mansour
- Penny Nymark
- Merlin Mei
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite|
This AOP was last modified on October 11, 2021 08:23
|Frustrated phagoytosis||August 13, 2019 04:48|
|Increased, secretion of proinflammatory and profibrotic mediators||October 19, 2021 14:22|
|Increased, recruitment of inflammatory cells||October 30, 2019 12:23|
|Increased, Reactive oxygen species||November 27, 2017 13:15|
|Increased, DNA damage and mutation||August 13, 2019 05:41|
|Genomic instability||July 06, 2021 06:05|
|Increase, Cell Proliferation||June 23, 2021 12:28|
|Increased, mesotheliomas||December 03, 2016 16:37|
|Frustrated phagoytosis leads to Increased proinflammatory mediators||July 06, 2021 06:10|
|Frustrated phagoytosis leads to Increased, Reactive oxygen species||July 06, 2021 06:11|
|Increased proinflammatory mediators leads to Recruitment of inflammatory cells||October 19, 2021 16:08|
|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|
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.
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|Sequence||Type||Event ID||Title||Short name|
|MIE||1668||Frustrated phagoytosis||Frustrated phagoytosis|
|KE||1497||Increased, recruitment of inflammatory cells||Recruitment of inflammatory cells|
|KE||1496||Increased, secretion of proinflammatory and profibrotic mediators||Increased proinflammatory mediators|
|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)
|Frustrated phagoytosis 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 phagoytosis leads to Increased, Reactive oxygen species||non-adjacent||High||Not Specified|
Life Stage Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Considerations for Potential Applications of the AOP (optional)
- 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.
- 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.
- 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.
- 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.
- 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.
- Chernova, Tatyana. ‘Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf)’, n.d., 20.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- ‘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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Wong, Raymond M. ‘Modulating Immunosuppression in the Intrapleural Space of Malignant Pleural Mesothelioma and Predictive Biomarkers to Guide Treatment Decisions’. Journal of Thoracic Oncology 11, no. 10 (1 October 2016): 1602–3. https://doi.org/10.1016/j.jtho.2016.07.019.
- Yamashita, Kyoko, Hirotaka Nagai, and Shinya Toyokuni. ‘Receptor Role of the Annexin A2 in the Mesothelial Endocytosis of Crocidolite Fibers’. Laboratory Investigation 95, no. 7 (July 2015): 749–64. https://doi.org/10.1038/labinvest.2015.28.
- Yoshikawa, Yoshie, Mitsuru Emi, Tomoko Hashimoto-Tamaoki, Masaki Ohmuraya, Ayuko Sato, Tohru Tsujimura, Seiki Hasegawa, et al. ‘High-Density Array-CGH with Targeted NGS Unmask Multiple Noncontiguous Minute Deletions on Chromosome 3p21 in Mesothelioma’. Proceedings of the National Academy of Sciences 113, no. 47 (22 November 2016): 13432–37. https://doi.org/10.1073/pnas.1612074113.
- Yoshikawa, Yoshie, Mitsuru Emi, Takashi Nakano, and Giovanni Gaudino. ‘Mesothelioma Developing in Carriers of Inherited Genetic Mutations’. Translational Lung Cancer Research 9, no. Suppl 1 (February 2020): S67–76. https://doi.org/10.21037/tlcr.2019.11.15.
- Yoshikawa, Yoshie, Ayuko Sato, Tohru Tsujimura, Mitsuru Emi, Tomonori Morinaga, Kazuya Fukuoka, Shusai Yamada, et al. ‘Frequent Inactivation of the BAP1 Gene in Epithelioid-Type Malignant Mesothelioma’. Cancer Science 103, no. 5 (2012): 868–74. https://doi.org/10.1111/j.1349-7006.2012.02223.x.
- Yu, Helen, Helen Pak, Ian Hammond-Martel, Mehdi Ghram, Amélie Rodrigue, Salima Daou, Haithem Barbour, et al. ‘Tumor Suppressor and Deubiquitinase BAP1 Promotes DNA Double-Strand Break Repair’. Proceedings of the National Academy of Sciences of the United States of America 111, no. 1 (7 January 2014): 285–90. https://doi.org/10.1073/pnas.1309085110.
- Zhang, Cheng-Zhong, Alexander Spektor, Hauke Cornils, Joshua M. Francis, Emily K. Jackson, Shiwei Liu, Matthew Meyerson, and David Pellman. ‘Chromothripsis from DNA Damage in Micronuclei’. Nature 522, no. 7555 (June 2015): 179–84. https://doi.org/10.1038/nature14493.
- Wils RS, Jacobsen NR, Vogel U, Roursgaard M, Møller P. Inflammatory response, reactive oxygen species production and DNA damage in mice after intrapleural exposure to carbon nanotubes. Toxicol Sci. 2021 Jun 4:kfab070. doi: 10.1093/toxsci/kfab070. Epub ahead of print. PMID: 34086969.
Kramara J, Osia B, Malkova A. Break-Induced Replication: The Where, The Why, and The How. Trends Genet. 2018 Jul;34(7):518-531. doi: 10.1016/j.tig.2018.04.002. Epub 2018 May 4. PMID: 29735283; PMCID: PMC6469874.
Snyder RJ, Verhein KC, Vellers HL, Burkholder AB, Garantziotis S, Kleeberger SR. Multi-walled carbon nanotubes upregulate mitochondrial gene expression and trigger mitochondrial dysfunction in primary human bronchial epithelial cells. Nanotoxicology. 2019 Dec;13(10):1344-1361. doi: 10.1080/17435390.2019.1655107. Epub 2019 Sep 3. PMID: 31478767; PMCID: PMC6879797.
Sakofsky CJ, Ayyar S, Deem AK, Chung WH, Ira G, Malkova A. Translesion Polymerases Drive Microhomology-Mediated Break-Induced Replication Leading to Complex Chromosomal Rearrangements. Mol Cell. 2015 Dec 17;60(6):860-72. doi: 10.1016/j.molcel.2015.10.041. Epub 2015 Dec 6. PMID: 26669261; PMCID: PMC4688117.