Related Experiment Video

Updated: Aug 9, 2026

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

Molecular nature of intrachromosomal deletions and base substitutions induced by environmental mutagens

Takehiko Nohmi1, Ken-ichi Masumura

  • 1Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan. nohmi@nihs.go.jp

Environmental and Molecular Mutagenesis
|January 26, 2005
PubMed

Insights

Environmental mutagens cause DNA damage. This study uses the gpt delta mouse model to analyze tissue-specific DNA alterations, revealing distinct deletion and base substitution patterns for various mutagens like radiation and chemicals.

Area of Science:

  • Molecular Biology
  • Genetics
  • Toxicology

Background:

  • Cellular DNA is constantly challenged by exogenous and endogenous mutagens.
  • Understanding DNA damage mechanisms requires analyzing specific molecular alterations in target tissues.
  • The gpt delta transgenic mouse model allows for detailed characterization of DNA damage, including deletions and base substitutions.

Purpose of the Study:

  • To characterize tissue-specific DNA alterations induced by various mutagens in vivo.
  • To elucidate the molecular mechanisms underlying deletion and base substitution induction by environmental agents.
  • To analyze intrachromosomal deletions and base substitutions induced by ionizing radiation, UVB, mitomycin C, PhIP, and APNH in gpt delta mice.

Main Methods:

  • Utilized the gpt delta transgenic mouse model to analyze DNA alterations.
  • Exposed mice to specific mutagens: carbon-ion radiation, UVB radiation, mitomycin C (MMC), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and aminophenylnorharman (APNH).
  • Analyzed tissue-specific intrachromosomal deletions (small and large) and base substitutions in liver, spleen, epidermis, bone marrow, and colon.

Main Results:

  • Carbon-ion radiation, UVB, and MMC induced large deletions (>1 kb), with about half occurring between direct repeats, suggesting nonhomologous end joining.
  • PhIP and APNH primarily induced 1 bp deletions in guanine runs.
  • UVB and MMC induced specific base substitutions (G:C-->A:T and tandem GG), while PhIP and APNH induced G:C-->T:A transversions, potentially involving translesion DNA synthesis.

Conclusions:

  • Different environmental mutagens induce distinct patterns of DNA deletions and base substitutions in a tissue-specific manner.
  • Mechanisms like nonhomologous end joining and translesion DNA synthesis are implicated in the observed DNA alterations.
  • Sequence information is crucial for understanding the in vivo mutagenic mechanisms of environmental agents.

More Related Videos

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter06:59

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Published on: March 31, 2022

Related Concept Videos

Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Mutations01:39

Mutations

Overview
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).