NDLI: An Adverse Outcome Pathway Network for Chemically Induced Oxidative Stress Leading to (Non)genotoxic Carcinogenesis.

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An Adverse Outcome Pathway Network for Chemically Induced Oxidative Stress Leading to (Non)genotoxic Carcinogenesis.

Content Provider	Europe PMC
Author	Veltman, Christina H. J. Pennings, Jeroen L. A. van de Water, Bob Luijten, Mirjam
Copyright Year	2023
Abstract	Nongenotoxic (NGTX) carcinogens induce cancer via othermechanismsthan direct DNA damage. A recognized mode of action for NGTX carcinogensis induction of oxidative stress, a state in which the amount of oxidantsin a cell exceeds its antioxidant capacity, leading to regenerativeproliferation. Currently, carcinogenicity assessment of environmentalchemicals primarily relies on genetic toxicity end points. Since NGTXcarcinogens lack genotoxic potential, these chemicals may remain undetectedin such evaluations. To enhance the predictivity of test strategiesfor carcinogenicity assessment, a shift toward mechanism-based approachesis required. Here, we present an adverse outcome pathway (AOP) networkfor chemically induced oxidative stress leading to (NGTX) carcinogenesis.To develop this AOP network, we first investigated the role of oxidativestress in the various cancer hallmarks. Next, possible mechanismsfor chemical induction of oxidative stress and the biological effectsof oxidative damage to macromolecules were considered. This resultedin an AOP network, of which associated uncertainties were explored.Ultimately, development of AOP networks relevant for carcinogenesisin humans will aid the transition to a mechanism-based, human relevantcarcinogenicity assessment that involves a substantially lower numberof laboratory animals.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC10283045&blobtype=pdf
ISSN	0893228X
Journal	Chemical Research in Toxicology [Chem Res Toxicol]
Volume Number	36
DOI	10.1021/acs.chemrestox.2c00396
PubMed Central reference number	PMC10283045
Issue Number	6
PubMed reference number	37156502
e-ISSN	15205010
Language	English
Publisher	American Chemical Society
Publisher Date	2023-05-08
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2023 The Authors. Published by American Chemical Society
Content Type	Text
Resource Type	Article
Subject	Medicine Toxicology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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