Related Experiment Video
Updated: May 17, 2026
11:24
Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
Adaptive radiation-induced epigenetic alterations mitigated by antioxidants
Autumn J Bernal1, Dana C Dolinoy, Dale Huang
1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina,, USA.
Summary
Low-dose ionizing radiation (LDIR) exposure in pregnant mice altered offspring epigenetics, specifically DNA methylation. Antioxidants countered these adaptive changes, suggesting LDIR
Area of Science:
- Epigenetics
- Radiation Biology
- Developmental Biology
Background:
- Humans encounter low-dose ionizing radiation (LDIR) from environmental and medical sources.
- LDIR is known to induce genetic mutations and may alter the epigenome.
- Epigenetic changes from early-life LDIR exposure can have adaptive or detrimental effects, influencing disease risk.
Purpose of the Study:
- To investigate the impact of LDIR on the epigenome, specifically DNA methylation.
- To determine if LDIR exposure during gestation leads to heritable epigenetic alterations.
- To explore the role of oxidative stress and potential mitigation by antioxidants.
Main Methods:
- Utilized the viable yellow agouti (A(vy)) mouse model.
- Exposed pregnant mice to varying doses of LDIR.
- Assessed DNA methylation at the A(vy) locus and observed offspring coat color.
- Administered maternal dietary antioxidant supplementation.
Main Results:
- LDIR significantly increased DNA methylation at the A(vy) locus in a sex-specific manner.
- Increased methylation was observed in male offspring exposed to 0.7–7.6 cGy LDIR, with peak effects at 1.4 and 3.0 cGy.
- Offspring coat color shifted towards pseudoagouti, and this effect was mitigated by maternal antioxidant supplementation.
Conclusions:
- LDIR exposure during gestation induces epigenetic alterations, leading to adaptive phenotypic changes.
- These adaptive changes appear to be mediated partly by oxidative stress, as they are negated by antioxidants.
- Findings suggest LDIR may play a role in radiation hormesis, challenging the notion that all radiation doses are harmful.
Related Concept Videos
01:38Nucleotide 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...
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...
01:08Nucleotide Excision Repair
Overview
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:25Bioactivation 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...
01:30Spontaneous 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).