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Related Concept Videos

Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
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Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Toxic Reactions: Overview01:26

Toxic Reactions: Overview

When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
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Toxicokinetics: Overview

Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...

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ExposoGraph: An Interactive Platform for Carcinogen Bioactivation and Detoxification Pathway Visualization.

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Related Experiment Video

Updated: May 17, 2026

A Web Tool for Generating High Quality Machine-readable Biological Pathways
08:01

A Web Tool for Generating High Quality Machine-readable Biological Pathways

Published on: February 8, 2017

ExposoGraph: An Interactive Platform for Carcinogen Bioactivation and Detoxification Pathway Visualization.

Julhash U Kazi1,2,3, Kenneth J Pienta4

  • 1Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, 22363, Sweden. kazi.uddin@med.lu.se.

Medical Oncology (Northwood, London, England)
|May 15, 2026
PubMed
Summary
This summary is machine-generated.

ExposoGraph integrates carcinogen exposure, metabolism, and genetic data into a knowledge graph. This tool aids in understanding gene-environment interactions for cancer risk assessment and hypothesis generation.

Keywords:
CarcinogenesisChemical carcinogenesisD3 HTMLGene-environment interactionInteractive platformKnowledge graphMetabolic activationNetwork visualizationPharmacogenomics

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A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
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A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information

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Related Experiment Videos

Last Updated: May 17, 2026

A Web Tool for Generating High Quality Machine-readable Biological Pathways
08:01

A Web Tool for Generating High Quality Machine-readable Biological Pathways

Published on: February 8, 2017

A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
05:01

A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information

Published on: July 1, 2020

Area of Science:

  • Bioinformatics
  • Genomics
  • Toxicology

Background:

  • Limited platforms unify carcinogenic exposures, metabolic activation/detoxification, DNA damage, and genetic annotations.
  • This gap hinders systematic evaluation of gene-environment interactions in cancer risk assessment.

Purpose of the Study:

  • To develop ExposoGraph, an interactive knowledge-graph platform for visualizing carcinogen metabolism and DNA damage pathways.
  • To integrate data from IARC, KEGG, PharmVar, CPIC, and CTD for a comprehensive reference graph.

Main Methods:

  • Developed an interactive knowledge graph integrating data on carcinogens, enzymes, metabolites, DNA adducts, and pathways.
  • The graph includes 98 nodes and 118 edges representing metabolic and DNA damage processes.
  • Implemented interactive features for filtering, searching, and detailed views with provenance and pharmacogenomic annotations.

Main Results:

  • The reference graph captures metabolic activation and detoxification pathways for 9 carcinogen classes and 15 index carcinogens.
  • It represents 38 enzymes across Phase I, II, and III metabolism, and DNA repair.
  • The androgen branch demonstrates cross-pathway connectivity, linking androgen metabolism to estrogen quinone formation and DNA adducts via CYP19A1.

Conclusions:

  • ExposoGraph provides an integrated framework linking carcinogenic exposures to metabolic fates and genetic modulators.
  • The platform facilitates hypothesis generation for gene-environment interaction studies.
  • It serves as a research tool to inform future individualized cancer risk modeling.