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Event: 1753

Key Event Title

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

Chronic reactive oxygen species

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

Chronic ROS

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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

Reactive oxygen species (ROS) are radicals, ions, or molecules that have a single unpaired electron in their outermost shell of electrons, which can be categorized into two groups: free oxygen radicals and non-radical ROS [Liou et al., 2010]. Free oxygen radicals include superoxide (O2^·-), hydroxyl radical (^·OH), nitric oxide (NO^·), organic radicals (R^·), peroxyl radicals (ROO^·), alkoxyl radicals (RO^·), thiyl radicals (RS^·), sulfonyl radicals (ROS^·), thiyl peroxyl radicals (RSOO^·), and disulfides (RSSR). Non-radical ROS include hydrogen peroxide (H₂O₂), singlet oxygen (¹O₂), ozone/trioxygen (O₃), organic hydroperoxides (ROOH), hypochlorite (ClO^-), peroxynitrite (ONOO^-), nitrosoperoxycarbonate anion (O=NOOCO₂^-), nitrocarbonate anion (O₂NOCO₂^-), dinitrogen dioxide (N₂O₂), nitronium (NO₂⁺), and highly reactive lipid- or carbohydrate-derived carbonyl compounds [Liou et al., 2010].

ROS are generated through NADPH oxidases consists of p47phox and p67phox. Arsenic produces ROS [Zhang et al., 2011]. The primary site of action for this event is DNA or proteins etc.

ROS play an important role in tumorigenesis [Zhang et al., 2011].

Chronic low-level increased ROS can alter the tumor microenvironment and promote cancer stem cell renewal, leading to therapeutic resistance [Gu et al., 2018].

The reason why this chronic ROS KE has been created is because it is important to have chronic ROS, but not just instant increased ROS, since ROS have a double-edged effect.

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

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Hydrogen peroxide (H₂O₂) can be detected with a colorimetric probe, which reacts with H₂O₂ in a 1:1 stoichiometry to produce a bright pink colored product, followed by the detection with a standard colorimetric microplate reader with a filter in the 540-570 nm range.

ROS in the blood can be detected using superparamagnetic iron oxide nanoparticles (SPION)-based biosensor [Lee et al., 2020].

ROS can be detected by fluorescent probes such as p-methoxy-phenol derivative [Ashoka et al., 2020].

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
response to reactive oxygen species	reactive oxygen species	increased

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
Molecular

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

Organ term
organ

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
Increases in ROS and chronic ROS leading to human treatment-resistant gastric cancer	MolecularInitiatingEvent	Agnes Aggy (send email)	Open for comment. Do not cite	EAGMST Under Review

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
Homo sapiens	Homo sapiens	Moderate	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	Moderate

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

Reactive oxygen species (ROS) are increased in human gastric cancer (Homo sapiens) [Gu et al., 2018].

References

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

Akai K, Tsuchiya K, Tokumura A, Kogure K, Ueno S, Shibata A, Tamaki T, Fukuzawa K. Free Radic Res. 2004 Sep;38(9):951-62. doi: 10.1080/1071576042000261945

Ashoka, A. H., Ali, F., Tiwari, R., Kumari, R., Pramanik, S. K., & Das, A. (2020). Recent Advances in Fluorescent Probes for Detection of HOCl and HNO. ACS omega, 5(4), 1730-1742. doi:10.1021/acsomega.9b03420

Gu, H., Huang, T., Shen, Y., Liu, Y., Zhou, F., Jin, Y., . . . Wei, Y. (2018). Reactive Oxygen Species-Mediated Tumor Microenvironment Transformation: The Mechanism of Radioresistant Gastric Cancer. Oxidative medicine and cellular longevity, 2018, 5801209-5801209. doi:10.1155/2018/5801209

Kruk J, Aboul-Enein H. Y. (2017). Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer TypesJournal Name: Mini-Reviews in Medicinal Chemistry, 17:11. doi:10.2174/1389557517666170228115324)

Lee, D. Y., Kang, S., Lee, Y., Kim, J. Y., Yoo, D., Jung, W., . . . Jon, S. (2020). PEGylated Bilirubin-coated Iron Oxide Nanoparticles as a Biosensor for Magnetic Relaxation Switching-based ROS Detection in Whole Blood. Theranostics, 10(5), 1997-2007. doi:10.7150/thno.39662

Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res. 2010 May;44(5):479-96. doi:10.3109/10715761003667554. PMID: 20370557; PMCID: PMC3880197.

Tsuchiya K, Akai K, Tokumura A, Abe S, Tamaki T, Takiguchi Y, Fukuzawa K. Biochim Biophys Acta. 2005 Aug 30;1725(1):111-9. doi:10.1016/j.bbagen.2005.05.001

Zhang, Z., Wang, X., Cheng, S., Sun, L., Son, Y.-O., Yao, H., . . . Shi, X. (2011). Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells. Toxicology and Applied Pharmacology, 256(2), 114-121. doi:10.1016/j.taap.2011.07.016