The biological significance of clustered DNA damage is not only based on the difficulty encountered by the different DNA repair proteins that process these closely spaced DNA lesions, but also to the fact that several of these OCDLs can be converted into de novo DSBs during repair . There are still many questions open as to which type of clusters will be more prone to be converted to potentially dangerous DSBs, but some parameters such as the presence of an SSB in one strand that delays the simultaneous process of other base lesions on the other strand, the nucleotide distance between the various lesions and the direction 3′ or 5′ to each other have been found to be critical .For example, some recent in vitro data using plasmid pUC18 DNA exposed to high-LET IR (He2+ or C6+ ions) or low-LET (X-rays) and under varying radical-scavenging conditions, suggest that base lesion clusters appear three or more base pairs apart and are promptly converted to a DSB by a glycosylase, regardless of the order of enzymatic treatment . These and other similar results are in good agreement with Monte Carlo (MC) track structure calculations, suggesting an increase of complexity with LET and specific base to SSB ratio etc. . Additionally, one cannot disregard that the initial repair steps at clustered damage sites is a major parameter that directs towards the conversion of MDS into DSB or not . Unrepaired clustered DNA lesions can lead to chromosomal breaks and significant GI as primarily manifested during the induction of clustered DNA damage by high-LET radiations .