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Event: 1821

Key Event Title

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

Decrease, Cell proliferation

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
Decrease, Cell proliferation
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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

Decreased cell proliferation describes the outcome of reduced cell division and cell growth. Cell proliferation is considered the main mechanism of tissue and organismal growth (Conlon 1999). Decreased cell proliferation has been associated with abnormal growth-factor signaling and cellular energy depletion (DeBerardinis 2008).

How It Is Measured or Detected

In the context of the EMOD/M2AOP prototyping, there are 2 components to the How it is Measured or Detected field, a structured component for adding Assay information and a free text component for unstructured descriptive information.In the free text field, include 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
Export Assays as CSV

Multiple types of in vitro bioassays can be used to measure this key event:

  • ToxCast high-throughput screening bioassays such as “BSK_3C_Proliferation”, “BSK_CASM3C_Proliferation” and “BSK_SAg_Proliferation” can be used to measure cell proliferation status.
  • Commercially available methods such as the well-established 5-bromo-2’-deoxyuridine (BrdU) (Raza 1985; Muir 1990) or 5-ethynyl-2’-deoxyuridine (EdU) assay. Both assays measure DNA synthesis in dividing cells to indicate proliferation status.

Observations 2.0

Observed meausures are instances of assay results that support this Key Event More help
ID Experimental Effect Biological Object Biological Process Method of Measurement Notes Evidence Source ID Citation (first author, year)

Observed Measures 1.0

Observed meausures are instances of assay results that support this Key Event More help
ID Stressor Sample (short_name) Assay Effect

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
cell proliferation cell decreased

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
Cell term
cell

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 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
Uncoupling of OXPHOS leading to growth inhibition 1 KeyEvent Allie Always (send email) Open for citation & comment WPHA/WNT Endorsed
Mitochondrial ATP synthase antagonism leading to growth inhibition (1) KeyEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite
Mitochondrial complex III antagonism leading to growth inhibition (1) KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite
Inhibition of Fyna leading to increased mortality KeyEvent Brendan Ferreri-Hanberry (send email) Open for citation & comment
Anatagonsim SMO leads to OFC KeyEvent Arthur Author (send email) Under development: Not open for comment. Do not cite Under Development
Uncoupling of OXPHOS leading to growth inhibition 5 KeyEvent Arthur Author (send email) Under development: Not open for comment. Do not cite Under Development
Decrease, GLI1/2 target gene expression leads to OFC KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite Under Development

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
zebrafish Danio rerio High NCBI
human Homo sapiens High NCBI
rat Rattus norvegicus High NCBI
mouse Mus musculus High NCBI

Life Stages

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

Sex Applicability

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

Evidence Supporting the Domain of Applicability

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

Taxonomic applicability domain

This key event is in general applicable to all eukaryotes, as most organisms are known to use cell proliferation to achieve growth.

Life stage applicability domain

This key event is in general applicable to all life stages. As cell proliferation not only occurs in developing organisms, but also in adults.

Sex applicability domain

This key event is sex-unspecific, as both genders use the same cell proliferation mechanisms.

References

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

Conlon I, Raff M. 1999. Size control in animal development. Cell 96:235-244. DOI: 10.1016/s0092-8674(00)80563-2.

DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. 2008. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism 7:11-20. DOI: https://doi.org/10.1016/j.cmet.2007.10.002.

Muir D, Varon S, Manthorpe M. 1990. An enzyme-linked immunosorbent assay for bromodeoxyuridine incorporation using fixed microcultures. Analytical Biochemistry 185:377-382. DOI: https://doi.org/10.1016/0003-2697(90)90310-6.

Raza A, Spiridonidis C, Ucar K, Mayers G, Bankert R, Preisler HD. 1985. Double labeling of S-phase murine cells with bromodeoxyuridine and a second DNA-specific probe. Cancer Research 45:2283-2287.