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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
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on May 26, 2024 20:39
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Deposition of Energy | March 08, 2024 11:49 |
Increase, DNA damage | May 08, 2019 12:28 |
Activation of Tumor Protein 53 | March 17, 2022 12:02 |
Increase risk, microcephaly | March 18, 2022 08:38 |
Premature cell differentiation | March 21, 2022 11:53 |
Apoptosis | February 28, 2024 09:40 |
decline, neural progenitor cells | January 10, 2024 04:44 |
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 |
Activation of TP53 leads to Premature differentiation | March 21, 2022 11:48 |
Activation of TP53 leads to Apoptosis | January 10, 2024 04:45 |
Apoptosis leads to decline, neural progenitor cells | January 10, 2024 04:46 |
Premature differentiation leads to decline, neural progenitor cells | January 10, 2024 04:46 |
decline, neural progenitor cells leads to Microcephaly | January 10, 2024 04:47 |
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 | 1979 | Premature cell differentiation | Premature differentiation |
KE | 1262 | Apoptosis | Apoptosis |
KE | 2200 | decline, neural progenitor cells | decline, neural progenitor cells |
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 |
Activation of TP53 leads to Premature differentiation | adjacent | Moderate | Not Specified |
Activation of TP53 leads to Apoptosis | adjacent | Moderate | Low |
Apoptosis leads to decline, neural progenitor cells | adjacent | High | Low |
Premature differentiation leads to decline, neural progenitor cells | adjacent | Low | Low |
decline, neural progenitor cells leads to Microcephaly | adjacent | High | Low |
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
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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