Figure 1.

DNA damage response (DDR) to double-strand DNA breaks (DSBs) in relation to acute radiation syndrome and late effects. DSBs caused by oxidative radicals are sensed by the MRN complex (MRE11–RAD50–NBS1), resulting in an ATM (ataxia-telangiectasia, mutated)-driven DDR. Gamma-H2AX (phosphorylated histone H2AX protein) is both a participant in the DDR and a marker of DSBs. Depending upon the dose of radiation, the type of radiation, the volume of tissue irradiated, and other factors, the DDR may lead to some combination of DNA repair, permanent cell cycle arrest (senescence), cell death, or survival with DNA damage. As a result of these processes, acute and late radiation effects may ensue, resulting in survival, death, or survival with late tissue damage. Note that “acute radiation syndrome” refers to the consequences of whole body radiation exposure. Acute effects of radiation may be limited to specific tissues or organs in the case of partial body radiation exposures or radiotherapy treatment to tumor-bearing tissue.