Event: 1753

Key Event Title


Chronic reactive oxygen species

Short name


Chronic ROS

Biological Context


Level of Biological Organization

Cell term


Organ term


Key Event Components


Process Object Action

Key Event Overview

AOPs Including This Key Event


AOP Name Role of event in AOP
Chronic ROS leading to human treatment-resistant gastric cancer MolecularInitiatingEvent



Taxonomic Applicability


Term Scientific Term Evidence Link
Homo sapiens Homo sapiens Moderate NCBI

Life Stages


Life stage Evidence
All life stages Moderate

Sex Applicability


Term Evidence
Unspecific High

Key Event Description


Site of action: The site of action for the molecular initiating event is DNA or proteins.

Reactive oxygen species (ROS) play an important role in tumorigenesis (Zhang et al., 2011).

ROS is generated through NADPH oxidases consists of p47phox and p67phox. Arsenic produces ROS (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).

How It Is Measured or Detected


・ROS in 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


ROS is increased in human gastric cancer (Homo sapiens) (Gu et al., 2018).

Evidence for Perturbation by Stressor

Overview for Molecular Initiating Event


Ionizing Radiation

Ionizing radiation induces reactive oxygen species.

(Ref. Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer Types

Author(s): Joanna Kruk, Hassan Y. Aboul-Enein*. Journal Name: Mini-Reviews in Medicinal Chemistry,

Volume 17 , Issue 11 , 2017, DOI : 10.2174/1389557517666170228115324)

ferric nitrilotriacetate

Iron(III)-nitrilotriacetate induces reactive oxygen species production via trasfer of an electron to molecular oxygen to form reactive oxygen species [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, 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

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

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:https://doi.org/10.1016/j.taap.2011.07.016