
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 441
Title
Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
Short name
Graphical Representation
Point of Contact
Contributors
- Olivier ARMANT
- Knut Erik Tollefsen
- Magda Sachana
- Brendan Ferreri-Hanberry
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite |
This AOP was last modified on July 16, 2022 18:37
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Deposition of Energy | October 26, 2021 13:04 |
Increase, DNA damage | May 08, 2019 12:28 |
Activation of Tumor Protein 53 | March 17, 2022 12:02 |
Increase, Apoptosis | April 15, 2017 16:17 |
Increase risk, microcephaly | March 18, 2022 08:38 |
Premature cell differentiation | March 21, 2022 11:53 |
Energy Deposition leads to Increase, DNA Damage | January 21, 2022 07:18 |
Energy Deposition leads to Microcephaly | March 17, 2022 12:16 |
Increase, DNA Damage leads to Activation of TP53 | March 09, 2022 08:20 |
Increase, Apoptosis leads to Microcephaly | March 17, 2022 12:14 |
Activation of TP53 leads to Increase, Apoptosis | March 09, 2022 08:22 |
Activation of TP53 leads to Premature differentiation | March 21, 2022 11:48 |
Premature differentiation leads to Microcephaly | March 21, 2022 11:49 |
Ionizing Radiation | May 07, 2019 12:12 |
Abstract
Exposures to ionizing radiations during the early phase of embryonic development can alter the process of brain development, increasing the risk of microcephaly. Excessive accumulation of DNA damages in cycling progenitors in the ventricular zone (VZ) and in the subventricular zone (SVZ) activates P53 leading primarily to cellular death via apoptosis and premature neuronal differentiation. Reduction of the progenitors pool consequently affect brain growth leading to microcephaly
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1686 | Deposition of Energy | Energy Deposition |
KE | 1194 | Increase, DNA damage | Increase, DNA Damage |
KE | 1974 | Activation of Tumor Protein 53 | Activation of TP53 |
KE | 1365 | Increase, Apoptosis | Increase, Apoptosis |
KE | 1979 | Premature cell differentiation | Premature differentiation |
AO | 1978 | Increase risk, microcephaly | Microcephaly |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Energy Deposition leads to Increase, DNA Damage | adjacent | High | Not Specified |
Increase, DNA Damage leads to Activation of TP53 | adjacent | High | Not Specified |
Increase, Apoptosis leads to Microcephaly | adjacent | High | Not Specified |
Activation of TP53 leads to Increase, Apoptosis | adjacent | High | Not Specified |
Activation of TP53 leads to Premature differentiation | adjacent | Moderate | Not Specified |
Premature differentiation leads to Microcephaly | adjacent | Moderate | Not Specified |
Energy Deposition leads to Microcephaly | non-adjacent | High | Not Specified |
Network View
Prototypical Stressors
Name |
---|
Ionizing Radiation |
Life Stage Applicability
Life stage | Evidence |
---|---|
Pregnancy | High |
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | High |
Overall Assessment of the AOP
Domain of Applicability
Term Scientific Term Evidence NCBI taxonid
mouse Mus musculus High 10090
human Homo sapiens High 9606
rat Rattus norvegicus High 10114