API XML

Aop: 115

AOP Title

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Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)

Short name:

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Epithelial cytotoxicity- forestomach tumor

Graphical Representation

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Click to download graphical representation template

Authors

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Cancer AOP group. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (wood.charles@epa.gov)

Point of Contact

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Charles Wood   (email point of contact)

Contributors

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  • Charles Wood

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
Increase, Cytotoxicity (epithelial cells) September 16, 2017 10:16
Increase, Inflammation September 16, 2017 10:14
Increase, Regenerative cell proliferation (forestomach epithelial cells) September 16, 2017 10:16
Increase, Hyperplasia (forestomach epithelial cells) September 16, 2017 10:16
Increase, Papillomas/carcinomas (squamous cells) September 16, 2017 10:16
Increase, Cytotoxicity (epithelial cells) leads to Increase, Inflammation December 03, 2016 16:38
Increase, Inflammation leads to Increase, Regenerative cell proliferation (forestomach epithelial cells) December 03, 2016 16:38
Increase, Regenerative cell proliferation (forestomach epithelial cells) leads to Increase, Hyperplasia (forestomach epithelial cells) December 03, 2016 16:38
Increase, Hyperplasia (forestomach epithelial cells) leads to Increase, Papillomas/carcinomas (squamous cells) December 03, 2016 16:38

Abstract

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This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 780 Increase, Cytotoxicity (epithelial cells) Increase, Cytotoxicity (epithelial cells)
2 KE 149 Increase, Inflammation Increase, Inflammation
3 KE 781 Increase, Regenerative cell proliferation (forestomach epithelial cells) Increase, Regenerative cell proliferation (forestomach epithelial cells)
4 KE 782 Increase, Hyperplasia (forestomach epithelial cells) Increase, Hyperplasia (forestomach epithelial cells)
5 AO 779 Increase, Papillomas/carcinomas (squamous cells) Increase, Papillomas/carcinomas (squamous cells)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increase, Cytotoxicity (epithelial cells) leads to Increase, Inflammation adjacent
Increase, Inflammation leads to Increase, Regenerative cell proliferation (forestomach epithelial cells) adjacent
Increase, Regenerative cell proliferation (forestomach epithelial cells) leads to Increase, Hyperplasia (forestomach epithelial cells) adjacent
Increase, Hyperplasia (forestomach epithelial cells) leads to Increase, Papillomas/carcinomas (squamous cells) adjacent

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Mus musculus Mus musculus NCBI
Rattus norvegicus Rattus norvegicus NCBI

Sex Applicability

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Sex Evidence
Male
Female

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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Proctor, D. M., Gatto, N. M., Hong, S. J., & Allamneni, K. P. (2007). Mode-of-action framework for evaluating the relevance of rodent forestomach tumors in cancer risk assessment. Toxicol Sci, 98(2), 313-326. doi: 10.1093/toxsci/kfm075