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Key Event Title
Chronic reactive oxygen species
|Level of Biological Organization|
Key Event Components
|response to reactive oxygen species||reactive oxygen species||increased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Chronic ROS leading to human treatment-resistant gastric cancer||MolecularInitiatingEvent||Shihori Tanabe (send email)||Open for comment. Do not cite||EAGMST Under Review|
|Homo sapiens||Homo sapiens||Moderate||NCBI|
|All life stages||Moderate|
Key Event Description
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
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].
Domain of Applicability
Reactive oxygen species (ROS) are increased in human gastric cancer (Homo sapiens) [Gu et al., 2018].
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