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Aop: 303

AOP Title

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Frustrated phagocytosis-induced lung cancer

Short name:

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Frustrated phagocytosis-induced lung cancer

Graphical Representation

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Click to download graphical representation template

Authors

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Carole Seidel

Sarah Valentino

Laurent Gaté

Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519 Vandœuvre, Cedex, France.

Point of Contact

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Carole Seidel   (email point of contact)

Contributors

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  • Carole Seidel
  • Sarah Valentino
  • Laurent GATE

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite


This AOP was last modified on August 13, 2019 04:39

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Revision dates for related pages

Page Revision Date/Time
Frustrated phagoytosis August 13, 2019 04:48
Release, Cytokine September 16, 2017 10:14
Increased, recruitment of inflammatory cells January 05, 2018 12:52
Increased, Reactive oxygen species November 27, 2017 13:15
Increased, DNA damage and mutation August 13, 2019 05:41
Increase, Cell Proliferation September 05, 2019 09:27
Lung cancer August 13, 2019 05:34
Frustrated phagoytosis leads to Release, Cytokine August 13, 2019 05:25
Release, Cytokine leads to Recruitment of inflammatory cells July 03, 2019 11:52
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 Increase, Cell Proliferation July 03, 2019 11:53
Increase, Cell Proliferation leads to Lung cancer July 03, 2019 11:53
High aspect ratio material August 13, 2019 04:38

Abstract

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Inhalation of materials, including fibres and particles, represents the main route of occupational exposure. The main issue is the biopersistance of these materials in lungs that could lead to chronic pulmonary pathologies such as fibrosis and cancer. Lung tumour is one of the most prevalent cancer in the world and, in general, is often detected at a late stage.

The knowledge related to the induction of lung disease following asbestos exposure led to study the toxicity of high aspect ratio materials (HARMs) in general. It is now well documented that exposure to HARMs could lead to pulmonary inflammation and ROS overproduction. Some studies suggest that lung biopersistence of HARMs is associated with frustrated phagocytosis and material length. The identified gaps regarding the induction of lung cancer following the exposure to HARMs is mainly on the interaction with cells, and no study demonstrated all the key events presented here in the same samples.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 1668 Frustrated phagoytosis Frustrated phagoytosis
2 KE 87 Release, Cytokine Release, Cytokine
3 KE 1497 Increased, recruitment of inflammatory cells Recruitment of inflammatory cells
4 KE 1115 Increased, Reactive oxygen species Increased, Reactive oxygen species
5 KE 1669 Increased, DNA damage and mutation Increased, DNA damage and mutation
6 KE 870 Increase, Cell Proliferation Increase, Cell Proliferation
7 AO 1670 Lung cancer Lung cancer

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Frustrated phagoytosis leads to Release, Cytokine adjacent
Release, Cytokine leads to Recruitment of inflammatory cells adjacent
Recruitment of inflammatory cells leads to Increased, Reactive oxygen species adjacent
Increased, Reactive oxygen species leads to Increased, DNA damage and mutation adjacent
Increased, DNA damage and mutation leads to Increase, Cell Proliferation adjacent
Increase, Cell Proliferation leads to Lung cancer adjacent

Network View

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Stressors

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Name Evidence Term
High aspect ratio material

Life Stage Applicability

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Life stage Evidence
Adult

Taxonomic Applicability

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Term Scientific Term Evidence Link
mammals mammals NCBI

Sex Applicability

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Sex Evidence
Unspecific

Overall Assessment of the AOP

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Domain of Applicability

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This AOP is applicable to adult (at least to mature lung tissue), to many vertebrate taxons, and to both genders.


Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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