BIOLOGICAL CONSEQUENCES OF NONHOMOGENEOUS ENERGY DEPOSITION BY IONIZING-RADIATION

The chemically reactive species produced by ionising radiation react within 2-3 nm of their site of origin causing locally multiply damaged sites (LMDS) (such as double strand breaks (DSBs)) on cellular DNA. As the LET of the radiation increases the numbers of individual damages in a LMDS increase. Since initial yields of DSBs show little dependence on LET, the higher RBE associated with higher LET radiation must be associated with the cell's ability to handle the damage - the nature of the damage is important. DSB repair studies do not assess the repair fidelity, this may be assessed at the molecular level by studies of mutation types produced: correct DSB rejoining, but with an error in base sequence would show as a point mutation in an exon. Degradation at DSB termini, nonhomologous recombinational repair or misrejoining of a DSB with the wrong DSB terminus would form a deletion.