Oxidative stress, DNA methylation and carcinogenesis
Rodrigo Franco1, Onard Schoneveld, Alexandros G Georgakilas
1Laboratory of Cell Biology and Signal Transduction, Biomedical Research Unit, FES-Iztacala, UNAM, Mexico, USA.
Cancer Letters
|March 29, 2008
Summary
Oxidative stress influences epigenetic changes, specifically DNA methylation patterns, during cancer development. Understanding these mechanisms is crucial for developing new cancer biomarkers and therapies.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Cellular transformation into malignancy involves phenotypic changes across cancer initiation, promotion, and progression.
- Gene expression alterations in cancer are linked to DNA methylation: hypermethylation represses tumor suppressors, while hypomethylation activates oncogenes.
- Reactive oxygen species (ROS)-induced oxidative stress is increasingly implicated in modulating these epigenetic processes.
Purpose of the Study:
- To explore the potential mechanisms by which oxidative stress influences epigenetic regulation of gene expression.
- To highlight the significance of understanding oxidative stress's role in cancer epigenetics.
Main Methods:
- Review of existing evidence on oxidative stress and epigenetic modifications in cancer.
- Hypothesizing potential modes of action for oxidative stress in modulating DNA methylation.
Main Results:
- Oxidative stress may directly or indirectly impact DNA methyltransferases and demethylases.
- Aberrant DNA methylation patterns, influenced by oxidative stress, are critical in carcinogenesis.
- Epigenetic alterations are key drivers of phenotypic changes during tumor development.
Conclusions:
- Oxidative stress plays a significant role in the epigenetic dysregulation observed in cancer.
- Aberrant DNA methylation patterns, modulated by oxidative stress, are vital for cancer diagnosis and prognosis.
- Further research into the interplay between oxidative stress and epigenetics can yield novel cancer biomarkers and therapeutic strategies.
Related Concept Videos
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).
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...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...