Whole-body responses to low-level radiation exposure: new concepts in mammalian radiobiology.

This review of low dose-induced whole-body effects, especially cancer, shows: 1) Biological systems appear in hierarchy levels of organization, from atoms to molecules, to cells, to tissues and organs, to the whole system; 2) System responses to low-level exposures depend on: quality and number of energy depositions in tissue micromasses (microdoses) being potential triggers to damage and protection; time interval between two microdose events per exposed micromass, that determines cellular responses to the preceding microdose; and responses to microdose events in the system being the target, with the balance between damage and benefit determining the net effect; 3) System responses to acute or chronic low-level exposures evolve from damage to the basic molecular level, mainly to DNA of stem cells, and from adaptive responses that may occur in the whole body. Damage may propagate to successive higher levels of organization, meeting protective barriers which may become upregulated by adaptive responses. The balance between damage and protection at each level per individual depends on tissue dose. At single tissue doses below congruent with 0.1 Gy net benefit tends to outweigh detriment. Thus, progression of damage to clinical disease is not linear; 4) Quality and extent of system responses are under genetic control. Thus, system net responses expectedly vary among individuals; 5) The balance between health risk and benefit of low-level exposure for a given individual may become predictable by gene-expression profiles in control and irradiated cells of this individual; and 6) Clinical trials applying individualized low-level irradiation are justified.