Related Experiment Video

Updated: Mar 8, 2026

Source and Route of Pyrrolizidine Alkaloid Contamination in Tea Samples
06:04

Source and Route of Pyrrolizidine Alkaloid Contamination in Tea Samples

Published on: September 28, 2022

2.6K

Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation

Peter P Fu1

  • 1National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, Arkansas 72079, United States.

Chemical Research in Toxicology
|January 18, 2017
PubMed

Insights

Pyrrolizidine alkaloids (PAs) are plant carcinogens. PA-derived DNA adducts may serve as biomarkers for PA exposure and liver tumor development, indicating a common activation pathway.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Biomarker Discovery

Background:

  • Pyrrolizidine alkaloids (PAs) are widespread plant-derived carcinogens.
  • Many PAs and their N-oxides exhibit cytotoxic, genotoxic, and tumorigenic properties.
  • A common genotoxic mechanism involving PA-derived DNA adducts in liver tumor initiation has been identified.

Purpose of the Study:

  • To report progress on the common metabolic activation pathway of PAs.
  • To propose the use of PA-derived DNA adducts as biomarkers for PA exposure and liver tumor formation.
  • To highlight the interconversion of reactive pyrrolic metabolites.

Main Methods:

  • Review of current research on PA metabolic activation.
  • Analysis of DNA adduct formation from various PAs.
  • Investigation of pyrrolic metabolite interconversion.

Main Results:

  • A common metabolic activation pathway for PAs leading to DNA adducts has been elucidated.
  • PA-derived DNA adducts are formed through interconverting pyrrolic metabolites.
  • These adducts show potential as biomarkers for PA exposure and liver carcinogenesis.

Conclusions:

  • PA-derived DNA adducts represent a common biological biomarker for PA exposure.
  • This pathway is crucial for understanding PA-induced liver tumor initiation.
  • Further research is needed to validate these adducts as biomarkers for liver tumor formation.

More Related Videos

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

14.4K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

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...
71
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
51
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
841
Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
5.4K
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...
2.1K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.8K