DNA-DAMAGE, REPAIR AND CHROMOSOMAL DAMAGE

An important question in radiobiology is the relationship between prim ary DNA damage and chromosomal aberrations. What determines the chromo somal aberration frequency, especially in radiosensitive cells? Much e vidence points to the double-strand break (dsb) as the critical lesion , however there is controversy over whether it is the initial inductio n, repair or residual dsb which determine of the level of expression o f chromosome damage. The picture is further complicated by the fact th at chromosome damage can be measured at several levels e.g. at metapha se, as micronuclei and as prematurely condensed chromosomes. Different ial frequencies of chromosome damage are measured in different cell li nes. Repair and residual dsb may play a role in metaphase aberrations when cells are exposed in G(1), but in irradiated G(2) cells the diffe rential frequencies do not depend on repair of dsb or on the residual level of dsb since a difference in the cell lines is observed at short intervals after irradiation, and in radiosensitive cell lines where t here is no deficiency in the repair of dsb, e.g. ataxia telangiectasia cells. Thus, at least in G(2) cells, a mechanism involving 'conversio n' of dsb into chromatid breaks is proposed. There are a number of pos sible reasons for high conversion of dsb into chromatid breaks includi ng altered chromatin structure, high chromosome condensation rates and covalent closure of chromosome ends.