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Sunday June 16, 2002 10:25 PM GMT

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Active oxygen species have long been known to be mutagenic, hence playing a role in cancer formation.

 
 

 
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Free Radicals; Types & Dangers
Antioxidants, classification and chemistry

 
   
 
     

The role of reactive oxygen species in DNA damage:

DNA base oxidation is a continuous process. Chromatin may offer some protection against oxidative DNA damage and specific repair processes may prevent or correct oxidative mutations. However, oxidants from both endogenous and exogenous sources can overwhelm these defences and mutagenesis can and does occur. Severe or prolonged exposure to oxidative stress can elicit all stages of carcinogenesis (Guyton and Kensler, 1993).

ROS involved in DNA damage:

It is now widely held that the mutagenic capacity of free radicals is due to the direct interaction of hydroxyl radicals (?OH) with DNA. Hydroxyl radicals have been detected by electron paramagnetic spectroscopy under conditions of active oxygen induced DNA damage. Hydrogen peroxide and superoxide do not directly interact with DNA to produce oxidative lesions in-vitro (Breimer, 1990). However, on interaction of these free radicals with transition metals the hydroxyl radical is produced which is responsible for DNA damage. In vitro both copper and iron can produce DNA damage by reactive oxygen species. Additional evidence is provided by the fact that metal chelators that block the elaboration of hydroxyl radicals can inhibit DNA damage, mutations, and malignant transformation induced by active oxygen species in cell-free and in cellular systems, as can agents that detoxify the hydroxyl radical or its precursors (Aruoma et al. 1989).

An unstable radical like the hydroxyl radical will react indiscriminately with all components of the DNA molecule. Hence, the hydroxyl radical causes DNA damage by direct interaction in the generation of many of its genetic lesions. However, it can also cause DNA damage by other methods e.g. stimulating the rise of calcium intracellularly which in turn stimulates endonucleases to cause strand breaks and degradation products from the DNA molecule.

Types of DNA damage produced by ROS:

The forms of DNA damage produced by ROS experimentally include the following:

  1. Modification of all bases.

  2. Production of base free sites.

  3. Deletions.

  4. Frameshifts.

  5. Strand breaks.

  6. DNA-protein cross-links.

  7. Chromosomal rearrangements.

(Halliwell et al. 1991)

 

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Fig. 3: The role of oxidants in multistage carcinogenesis (Harris 1989). 

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