Target intelligence / Profile preview

Radiation-induced DNA radicals and DNA damage intermediates (DNA radicals)

Target
DNA radicals
Molecular classification
Free radicals, Nucleic acid lesions, Reactive oxygen species (ROS) products, Other
01

Overview

Radiation-induced DNA radicals and DNA damage intermediates are highly reactive chemical species formed when ionizing radiation interacts with cellular DNA, either through direct ionization or indirectly via the radiolysis of water. These intermediates include base-centered radicals (such as the guanine cation radical), sugar-centered radicals, and various oxidative lesions like abasic sites and clustered damage. If these transient radicals are not neutralized, they can react with oxygen to form permanent, non-restorable lesions (the oxygen fixation hypothesis) or undergo chemical reactions leading to single-strand and lethal double-strand breaks. In clinical practice, these intermediates are the primary targets for radioprotective agents like amifostine, which scavenge free radicals and donate hydrogen atoms to chemically restore the DNA. Conversely, radiosensitizers aim to stabilize these radicals or exploit hypoxic environments to enhance the lethality of radiation in tumor cells. Understanding the kinetics and repair of these intermediates is fundamental to optimizing radiotherapy and developing countermeasures for radiation-induced toxicities.

Other names
DNA free radicalsDNA lesionsOxidative DNA damageRadiation-induced DNA damageDNA damage products
02

Biological functions

DNA damageCell deathApoptosisMutagenesisSignal transductionCell cycle arrest
03

Disease associations

CancerRadiation sickness (Acute Radiation Syndrome)XerostomiaFibrosisMucositisAging
04

Safety considerations

HypotensionNausea and vomitingPotential for unintended tumor protectionSystemic toxicity of radiosensitizersShort therapeutic window due to radical half-life
05

Interacting drugs

Amifostine (WR-2721)

7 more in the full profile.

06

Biomarkers

8-Oxo-2-deoxyguanosine (8-OHdG)gamma-H2AX (H2AFX)53BP1 fociComet assay parametersAlkaline phosphatase activity

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