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Event: 1669

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, DNA damage and mutation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased, DNA damage and mutation
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
DNA damage response, detection of DNA damage site of DNA damage increased
mutation increased
chromosome breakage chromosome increased
chromosomal instability chromosome increased
abnormal DNA repair DNA repair complex increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Frustrated phagocytosis-induced lung cancer KeyEvent Carole Seidel (send email) Under development: Not open for comment. Do not cite Under Development
Frustrated phagocytosis leads to malignant mesothelioma KeyEvent Penny Nymark (send email) Under development: Not open for comment. Do not cite
AHR activation leading to lung cancer via IL-6 tox path KeyEvent Dianke Yu (send email) Under development: Not open for comment. Do not cite
AHR activation leading to lung cancer via AHR-ARNT tox path KeyEvent Dianke Yu (send email) Under development: Not open for comment. Do not cite
DNA damage and metastatic breast cancer MolecularInitiatingEvent Usha Adiga (send email) Under development: Not open for comment. Do not cite Under Development
Interaction with lung cells leads to lung cancer KeyEvent Penny Nymark (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.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 in relation to this KE. More help
Term Scientific Term Evidence Link
mammals mammals NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

DNA damages are alteration of the DNA backbone including abasic site, single or double strand breaks or inter-strand crosslinks. These damages could be recognized and repaired by specialized enzymes. However, if damages persist, mutation in the DNA sequences can occur. Unlike DNA damages, DNA mutations when both strands are modified cannot be repaired and are heritable. Mutations affect the genotype and could affect phenotype.

Different mechanisms are implicated in DNA damage such as oxidative burst, DNA repair dysfunction or centrosome amplification and chromosome instability [1].

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

DNA damages could be measured using different assays, such as micronucleus formation (OECD n°487) [2], comet assay with different protocols for the detection of double and single-strand breaks, DNA-DNA and DNA-protein crosslinks, adduct and oxidized nucleotides (OECD n°489) [3, 4] and γH2AX for the analysis of DNA strand breaks [5].

DNA mutation could be analyzed with Ames test or via the analysis of frequencies of mutations (OECD n°471) [6].

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

The DNA damages and mutations can occur in mammals, male or female, and is generally measured in adults.

References

List of the literature that was cited for this KE description. More help

1.         Zhang Y. Cell toxicity mechanism and biomarker. 2018;7 1:34; doi: 10.1186/s40169-018-0212-7.

2.         Kato T, Totsuka Y, Ishino K, Matsumoto Y, Tada Y, Nakae D, et al. Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems. Nanotoxicology. 2013;7 4:452-61; doi: 10.3109/17435390.2012.674571.

3.         Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, et al. Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. 2008;116 9:1211-7; doi: 10.1289/ehp.10924.

4.         Hiraku Y, Guo F, Ma N, Yamada T, Wang S, Kawanishi S, et al. Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation. Particle and fibre toxicology. 2016;13:16; doi: 10.1186/s12989-016-0127-7.

5.         Catalan J, Siivola KM, Nymark P, Lindberg H, Suhonen S, Jarventaus H, et al. In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes. Nanotoxicology. 2016;10 6:794-806; doi: 10.3109/17435390.2015.1132345.

           6.         Fukai E, Sato H, Watanabe M, Nakae D, Totsuka Y. Establishment of an in vivo simulating co-culture assay            platform for genotoxicity of multi-walled carbon nanotubes. Cancer science. 2018; doi: 10.1111/cas.13534.