THE COMPLEXITY OF DNA-DAMAGE - RELEVANCE TO BIOLOGICAL CONSEQUENCES

Ionizing radiation causes both singly and multiply damaged sites in DN A when the range of radical migration is limited by the presence pf hy droxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challen ges they present to cellular repair mechanisms. These sites occur in t he form of DNA double-strand breaks (dsb) but also as other multiple d amages that can be converted to dsb during attempted repair. The prese nce of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong p artner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics.) The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scaven gable and non-scavengable mechanisms. The yields of complex damages ca n in turn be used to support the conclusion that cellular mutations ar e a consequence of the presence of these damages within a gene. Litera ture data are used to support these statements and to develop overall mechanisms connecting the production of primary species to the product ion of biologically relevant damages. The consequences of the LET of t he radiation on multiplicity of damage are discussed and suggestions m ade for the cause of the decrease of the oxygen enhancement ratio as t he LET increases.