Related Experiment Video

Updated: Aug 23, 2026

Identification Of Erythromyeloid Progenitors And Their Progeny In The Mouse Embryo By Flow Cytometry
08:59

Identification Of Erythromyeloid Progenitors And Their Progeny In The Mouse Embryo By Flow Cytometry

Published on: July 17, 2017

Genotoxic mechanism of tamoxifen in developing endometrial cancer

Sung Yeon Kim1, Naomi Suzuki, Y R Santosh Laxmi

  • 1Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA.

Drug Metabolism Reviews
|July 9, 2004
PubMed

Insights

Tamoxifen (TAM) increases endometrial cancer risk by forming DNA adducts, leading to mutations. Toremifene may be a safer alternative due to inhibited DNA reactivity.

Area of Science:

  • Pharmacology
  • Genotoxicology
  • Oncology

Background:

  • Tamoxifen (TAM) is a widely used breast cancer drug.
  • TAM use is linked to an increased risk of endometrial cancers.
  • Genotoxic DNA damage by TAM metabolites is a suspected cause.

Purpose of the Study:

  • To review the mechanism of TAM-DNA adduct formation.
  • To describe the mutagenic events associated with TAM-DNA adducts.
  • To discuss the detection of TAM-DNA adducts in women treated with TAM.

Main Methods:

  • Overview of TAM metabolism by cytochrome P450 3A4 and hydroxysteroid sulfotransferase.
  • Description of reactive intermediate formation and DNA adduct generation.
  • Analysis of mutagenic potential (G-->T transversions) and K-ras gene mutations.

Main Results:

  • TAM metabolites form alpha-(N2-deoxyguanosinyl)tamoxifen adducts with DNA.
  • These adducts induce G-->T transversions, observed in K-ras codon 12.
  • TAM-DNA adducts are detectable in the endometrium of treated women.

Conclusions:

  • TAM-DNA adducts are implicated in endometrial cancer development.
  • Toremifene shows reduced reactivity with DNA, suggesting it as a safer alternative.
  • Understanding TAM's genotoxicity is crucial for risk assessment and alternative drug development.

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

Related Concept Videos

Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
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...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Oogenesis02:07

Oogenesis

In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
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...