Indirect DNA damage

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Indirect DNA Damage[edit | edit source]

Illustration of indirect DNA damage

Indirect DNA damage refers to the harm caused to the DNA molecule not by direct interaction with a damaging agent, but through secondary processes. This type of damage is often mediated by reactive species generated as a result of exposure to various environmental factors, such as ultraviolet radiation, ionizing radiation, and certain chemical agents.

Mechanisms of Indirect DNA Damage[edit | edit source]

Indirect DNA damage typically involves the generation of reactive oxygen species (ROS) or other reactive intermediates that can interact with DNA. These reactive species are often produced as a result of the interaction of radiation or chemicals with cellular components, such as water or lipids.

Reactive Oxygen Species[edit | edit source]

Reactive oxygen species can cause DNA damage

Reactive oxygen species, including superoxide, hydroxyl radicals, and hydrogen peroxide, are highly reactive molecules that can cause a variety of DNA lesions. These lesions include base modifications, single-strand breaks, and double-strand breaks.

Radiation-Induced Damage[edit | edit source]

Ionizing radiation can lead to the formation of ROS through the radiolysis of water, which is abundant in biological tissues. The ROS generated can then diffuse and interact with DNA, causing indirect damage. This is a significant concern in radiation therapy and radiation protection.

Chemical Agents[edit | edit source]

Certain chemicals, such as polycyclic aromatic hydrocarbons and tobacco smoke, can also lead to the production of reactive intermediates that cause indirect DNA damage. These chemicals may undergo metabolic activation in the body, leading to the formation of DNA-reactive species.

Consequences of Indirect DNA Damage[edit | edit source]

Indirect DNA damage can lead to mutations if the lesions are not properly repaired by the cell's DNA repair mechanisms. These mutations can contribute to the development of cancer and other diseases. The cell has several repair pathways, such as base excision repair and nucleotide excision repair, to address different types of DNA damage.

Prevention and Mitigation[edit | edit source]

To minimize indirect DNA damage, it is important to limit exposure to known sources of ROS and other reactive species. This includes using sunscreen to protect against UV radiation, avoiding smoking, and minimizing exposure to environmental pollutants. Antioxidants, both endogenous and dietary, can also help neutralize ROS and protect DNA from damage.

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Contributors: Prab R. Tumpati, MD