Low-dose cancer risk modeling must recognize up-regulation of protection.

IONIZING RADIATION PRIMARILY PERTURBS THE BASIC MOLECULAR LEVEL PROPORTIONAL TO DOSE, WITH POTENTIAL DAMAGE PROPAGATION TO HIGHER LEVELS: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation.

Nuclear energy and health: and the benefits of low-dose radiation hormesis.

Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed.

Radiobiological basis of low-dose irradiation in prevention and therapy of cancer.

Antimutagenic DNA damage-control is the central component of the homeostatic control essential for survival. Over eons of time, this complex DNA damage-control system evolved to control the vast number of DNA alterations produced by reactive oxygen species (ROS), generated principally by leakage of free radicals from mitochondrial metabolism of oxygen. Aging, mortality and cancer mortality are generally accepted to be associated with stem cell accumulation of permanent alterations of DNA, i.

Low-dose radioimmuno-therapy of cancer.

Four decades of genomic, cellular, animal and human data have shown that low-dose ionizing radiation stimulates positive genomic and cellular responses associated with effective cancer prevention and therapy and increased life span of mammals and humans.( 1-8) Nevertheless, this data is questioned because it seems to contradict the well demonstrated linear relation between ionizing radiation dose and damage to DNA without providing a clear mechanistic explanation of how low-dose radiation could produce such beneficial effects. This apparent contradiction is dispelled by current radiobiology that now includes DNA damage both from ionizing radiation and from endogenous metabolic free radicals, and coupled with the biological response to low-dose radiation.

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.

Responses to low doses of ionizing radiation in biological systems.

Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.

Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage.

Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation down to zero-dose constitutes the linear-no-threshold (LNT) hypothesis of radiation-induced cancer incidence.