Update on target theory as applied to chromosomal aberrations

Abstract

The early radiobiologists, who developed target theory to explain their results, considered the chromosome "target" as a visible thread that could be physically broken by ionizing radiation. Most of the broken ends restituted, but those that did not were free to wander about and, within limits, could rejoin with any other broken end they happened to contact to form structural aberrations. Failing this, they could remain to be seen as "open" breaks at the subsequent metaphase. These ideas, and their inevitable consequences, still form the basis for much modern thinking, even though we now known that the structure of the chromosome, and of the interphase nucleus, are very much more complicated than the originators of the theory envisaged. Current understanding of chromosomes at the molecular level and the varied responses a cell can mobilize when damage is introduced, raise again the question, Can we still think in terms of simple targets? Some of the experimental observations and suggestions made since those early days are reviewed, and the application of target theory to the three theories of aberration origins (Classic, Exchange, Recombination) is briefly discussed.

Abnormal Blood Levels of Trace Elements and Metals, DNA Damage, and Breast Cancer in the State of Kuwait

“…MN formation reflects chromosome abnormalities, and there is evidence supporting the notion that the latter are a direct consequence and manifestation of damage at the DNA level [66][67][68][69]. For instance, chromosome breaks may result from unrepaired double strand breaks in DNA, and chromosome rearrangements may result from misrepair of strand breaks in DNA [66]. It is also recognized that chromosome loss and malsegregation of chromosomes (nondisjunction) are an important event in cancer and that they are caused by defects in the spindle, centromere, or as a consequence of undercondensation of chromosome structure before metaphase [67][68][69].…”

“…Data are accumulating that support the hypothesis that genotoxicity endpoints are predictors of human cancer risk [65]. MN formation reflects chromosome abnormalities, and there is evidence supporting the notion that the latter are a direct consequence and manifestation of damage at the DNA level [66][67][68][69]. For instance, chromosome breaks may result from unrepaired double strand breaks in DNA, and chromosome rearrangements may result from misrepair of strand breaks in DNA [66].…”

M-FISH analysis shows that complex chromosome aberrations induced by α-particle tracks are cumulative products of localized rearrangements

“…It is known that densely ionizing ␣-particles are capable of inducing multiple sites of DNA damage in a localized volume (26), thus key to the formation of these cycles are questions that relate to the organization of chromatin at the time of damage (31,32). In other words, are breaks induced in chromatin loops of preexisting functional associations, or do damaged ends mobilize to form ''chromatin aggregates'' that function as ''repair centers''?…”

Genotoxic and cytotoxic effects of formic acid on human lymphocytes in vitro

“…Chromosome aberrations occur due to damage at the DNA level. For instance, chromosome breaks may be caused by unrepaired double chain breaks in the DNA, and the emergence of chromosomes with a new structure may be caused by the false repair of chain breaks in the DNA (13).…”