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AOP: 326
Title
Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death
Short name
Graphical Representation
Point of Contact
Contributors
- You Song
- Li Xie
- Knut Erik Tollefsen
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 October 08, 2024 06:28
Revision dates for related pages
Page | Revision Date/Time |
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Increase, Reactive Oxygen Species | October 08, 2024 03:52 |
Increase, Protein oxidation | April 30, 2020 12:37 |
Increase, Cell injury/death | May 27, 2024 07:23 |
Decrease, Growth | July 06, 2022 07:36 |
Increase, ROS leads to Increase, Protein oxidation | April 30, 2020 12:38 |
Increase, Protein oxidation leads to Cell injury/death | October 08, 2024 04:26 |
Cell injury/death leads to Decrease, Growth | September 27, 2022 13:22 |
Heavy metals (cadmium, lead, copper, iron, nickel) | October 25, 2021 03:21 |
Abstract
A wide variety of chemicals can induce the formation of reactive oxygen species (ROS), disrupting the cellular redox balance. These chemicals interact with cellular components, including mitochondria and enzymes like cytochrome P450, leading to the generation of superoxide anions, hydrogen peroxide, and hydroxyl radicals. Once produced, ROS can oxidize lipids, proteins, and nucleic acids, resulting in cellular damage and contributing to oxidative stress. The extent of ROS production is influenced by factors such as the chemical structure, the efficiency of cellular defense mechanisms, and the presence of metal ions that can catalyze ROS formation.
Over time, excessive ROS generation can overwhelm antioxidant defenses, causing oxidative damage to essential macromolecules, including DNA, lipids, and proteins, as well as critical cellular components like the plasma membrane and mitochondria. Oxidative DNA damage is a direct consequence of excessive ROS formation. One of the most common oxidative modifications, 8-oxoguanine (8-oxoG), can mispair with adenine during DNA replication, leading to G to T transversions, a specific type of mutation.
Moreover, oxidative DNA damage can trigger cell death through several interconnected mechanisms, such as apoptosis (programmed cell death) and necrosis (uncontrolled cell death). Cell population dynamics plays a crucial role in regulating tissue and organismal growth.
As part of a large AOP network linking ROS to growth inhibition, this AOP mainly describes how excessive ROS formation leads to growth inhibtion via induction of oxidative protein damage and cell death.
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 |
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MIE | 257 | Increase, Reactive Oxygen Species | Increase, ROS |
KE | 1767 | Increase, Protein oxidation | Increase, Protein oxidation |
KE | 55 | Increase, Cell injury/death | Cell injury/death |
AO | 1521 | Decrease, Growth | Decrease, Growth |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Increase, ROS leads to Increase, Protein oxidation | adjacent | High | |
Increase, Protein oxidation leads to Cell injury/death | adjacent | High | |
Cell injury/death leads to Decrease, Growth | adjacent | Moderate |
Network View
Prototypical Stressors
Life Stage Applicability
Life stage | Evidence |
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Not Otherwise Specified |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
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fish | fish | NCBI |
Sex Applicability
Sex | Evidence |
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Unspecific |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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