Damage amplification

Damage Amplification Reaction of DNA Radical Intermediates with Proximal DNA Bases and Sugars... 

Mechanistically, this damage amplification reaction is not yet understood. Obviously, a second dAdo molecule is required for the reaction to proceed. When the termination of the radicals becomes very fast, this reaction no longer can proceed efficiently. As a consequence, the yields of 5, 8-cyclo-dAdo and 5 -CHO-dAdo drop dramatically at very high dose rate, i.e., under the conditions of pulse radiolysis (Fig. 10.1, triangles Wagner et al. 1999). This is one of the reasons, why this reaction cannot be studied with this technique. 

This type of damage amplification reaction is also observed in polynucleotides and in DNA (Chaps 11.2 and 12.5). 

Carter KN, Taverner T, SchiesserCH, Greenberg MM (2000) Chemical evidence for thiyl radical addition to the C6-position of a pyrimidine nucleoside and its possible relevance to DNA damage amplification. J Org Chem 65 8375-8378... 

Clustered Lesions and Damage Amplification Reactions (Tandem Lesions) 391... 

Another damage amplification reaction has been observed with a dinucleotide model which allowed to generate a Thy-5-yl radical specifically. In the presence of 02, it causes the formation of the 2-dRL lesion at the adjacent nucleotide unit (Chap. 10.3). Based on this, -OH-addition to C(6) of T and C could give rise to this tandem lesion also in DNA (as yet not detected). 

It has thus been concluded that the chemical repair, that is in competition with a reaction of the DNA radicals with Oj, may reduce the severity of DNA damage by preventing damage amplification reactions induced by peroxyl radicals (see below). 

TaUman KA, Greenberg MM. Oxygen-dependent DNA damage amplification involving 5,6-dihydrothymidin-5-yl in a strucmraUy minimal system. J Am Chem Soc. 2001 123 5181-5187. 

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