Critical DNA target size model of ionizing radiation-induced mammalian cell death.

A new model of mammalian cell killing by ionizing radiation is presented. This model, termed the critical DNA target size model, postulates that DNA double-strand breakage is the critical radiation-induced lesion and that the dose-response for such breakage can be non-linear due to the action of a saturable chemical repair process. DNA double-strand breakage occurring within critical targets (proto-oncogene- or common fragile site-associated sequences) is postulated to initiate recombination events with undamaged sequences, leading to chromosomal aberrations. The subsequent loss of acentric fragments at mitosis is postulated to prevent the continuity of the genome and to produce cell death by the induction of chromatin structural changes. Experimental evidence contrary to other radiation action models is examined, and the hypotheses of the model are justified.