Aop: 432

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

Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
Ionizing Radiation-Induced AML

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
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Authors

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

Kimberly Appelgate1, Christophe Badie2, Dag Anders Brede3, Fieke Dekkers4,5,, Maria Gomolka6, Dmitry Klokov7,8,Yevgeniya Le9,10, Katalin Lumniczky11

1Radiology, University of Kentucky College of Medicine, Lexington, 40506-9983, UNITED STATES.

2Christophe Badie/Cancer Mechanisms and Biomarkers group/Radiation Effects Department/Radiation, Chemical & Environmental Hazards/Harwell Campus

Chilton, Didcot, Oxfordshire OX11 ORQ United Kingdom/ UK Health Security Agency     

3Centre for Environmental Radioactivity (CERAD), Faculty of Environmental Sciences and Natural Resource Management (MINA), Norwegian University of Life Sciences (NMBU), 1432 Ås, Norway.

4Mathematical Institute, Utrecht University, Utrecht, 3508 TA, The Netherlands.

5Netherlands National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

6Federal Office for Radiation Protection│ Radiationbiology │ WR1 Ingolstädter Landstr.1

85764 Oberschleissheim

7Experimental Radiotoxicology and Radiobiology Laboratory, Institute for Radiological Protection and Nuclear Safety, 92262 Fontenay-aux-Roses, France.

8Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

9Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

10Radiobiology and Health, Canadian Nuclear Laboratories, Chalk River, ON, Canada.

11Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, Hungary.

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
Dag Anders Brede   (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
  • Dag Anders Brede
  • Kimberly Applegate
  • Maria Gomolka
  • Dmitry Klokov
  • Katalin Lumniczky
  • Christophe Badie

Status

Provides users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. OECD Status - Tracks the level of review/endorsement the AOP has been subjected to. OECD Project Number - Project number is designated and updated by the OECD. SAAOP Status - Status managed and updated by SAAOP curators. More help
Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite
This AOP was last modified on August 18, 2022 04:35

Revision dates for related pages

Page Revision Date/Time
Deposition of Energy October 26, 2021 13:04
Increase in reactive oxygen and nitrogen species (RONS) May 08, 2019 12:30
Increase, DNA damage May 08, 2019 12:28
Increased Pro-inflammatory mediators July 12, 2022 08:59
Increase, Mutations in Critical Genes September 16, 2017 10:16
Acute Myeloid Leukemia December 03, 2021 07:45
Inadequate DNA repair October 26, 2021 08:25
Increase, Cell Proliferation June 23, 2021 12:28
Suppression, Immune system December 03, 2016 16:37
Ionizing Radiation May 07, 2019 12:12

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

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 1686 Deposition of Energy Energy Deposition
KE 1632 Increase in reactive oxygen and nitrogen species (RONS) Increase in RONS
KE 1194 Increase, DNA damage Increase, DNA Damage
KE 155 Inadequate DNA repair Inadequate DNA repair
KE 876 Increase, Mutations in Critical Genes Increase, Mutations in Critical Genes
KE 870 Increase, Cell Proliferation Increase, Cell Proliferation
KE 1493 Increased Pro-inflammatory mediators Increased pro-inflammatory mediators
KE 403 Suppression, Immune system Suppression, Immune system

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

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

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
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens NCBI
Mus musculus Mus musculus NCBI

Sex Applicability

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

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

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