API XML

Aop: 108

AOP Title

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Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)

Short name:

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PDK inhibition- HCC

Graphical Representation

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Click to download graphical representation template

Authors

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Cancer AOP Workgroup. 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 Do not cite 1.29 Under Development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, Adenomas/carcinomas (hepatocellular) September 16, 2017 10:16
Increase, Cytotoxicity September 16, 2017 10:16
Peptide Oxidation November 13, 2017 10:22
Increased, Induction of pyruvate dehydrogenase (PDH) December 03, 2016 16:37
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme December 03, 2016 16:37
Increase, Oxidative metabolism December 03, 2016 16:37
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme leads to Increased, Induction of pyruvate dehydrogenase (PDH) December 03, 2016 16:37
Increased, Induction of pyruvate dehydrogenase (PDH) leads to Increase, Oxidative metabolism December 03, 2016 16:38
Increase, Oxidative metabolism leads to Peptide Oxidation December 03, 2016 16:38
Peptide Oxidation leads to Increase, Cytotoxicity December 03, 2016 16:38
Increase, Cytotoxicity leads to Increase, Adenomas/carcinomas (hepatocellular) 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 724 Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme
2 KE 768 Increase, Cytotoxicity Increase, Cytotoxicity
3 KE 209 Peptide Oxidation Peptide Oxidation
4 KE 726 Increased, Induction of pyruvate dehydrogenase (PDH) Increased, Induction of pyruvate dehydrogenase (PDH)
5 KE 769 Increase, Oxidative metabolism Increase, Oxidative metabolism
6 AO 719 Increase, Adenomas/carcinomas (hepatocellular) Increase, Adenomas/carcinomas (hepatocellular)

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme leads to Increased, Induction of pyruvate dehydrogenase (PDH) adjacent
Increased, Induction of pyruvate dehydrogenase (PDH) leads to Increase, Oxidative metabolism adjacent
Increase, Oxidative metabolism leads to Peptide Oxidation adjacent
Peptide Oxidation leads to Increase, Cytotoxicity adjacent
Increase, Cytotoxicity leads to Increase, Adenomas/carcinomas (hepatocellular) 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

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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U.S. Environmental Protection Agency (Aug 2003). Toxicological Review of Dichloroacetic Acid: In Support of Summary Information on the Integrated Risk Information System (IRIS) (Vol. EPA 635/R-03/007). Washington, DC