Cellular signal adaptation with damage control at low doses versus the predominance of DNA damage at high doses.
Ionizing radiation is known to potentially interfere with cellular functions at all levels of cell organization and induces DNA lesions apparently with an incidence linearly related to D, also at low doses. On the other hand, low doses have also been observed to initiate a slowly appearing temporary protection against causation and accumulation of DNA lesions, involving the radical detoxification system, DNA repair and removal of DNA damage. This protection apparently does not operate at high doses; it has been described to be nonlinear, increasing initially with D, beginning to decrease when D exceeds approximately 0.1-0.2 Gy, and eventually disappearing at higher D. The various adaptive responses have been shown to last individually from hours to weeks in different cell types and resemble responses to oxidative stress. Damage to DNA is continuously and endogenously produced mainly by reactive oxygen species (ROS) generated in a normal oxidative metabolism. This endogenous DNA damage quantitatively exceeds DNA damage from low-dose irradiation, by several orders of magnitude. Thus, the protective responses following acute low-dose irradiation may be presumed to mainly counteract the endogenous DNA damage. Accordingly, the model described here uses two dose-effect functions, a linear one for causing and a nonlinear one for protecting against DNA damage from whatever cause in the irradiated cells and tissues. The resulting net dose-risk function strongly suggests that the incidence of cancer versus dose in the irradiated tissues is much less likely to be linear than to exhibit a threshold. The observed cancer incidence may even fall below the spontaneous incidence, when D to cells is below approximately 0.2 Gy. However incomplete, these data support a reexamination of the LNT hypothesis.
Feinendegen
L E
LE
Department of Nuclear Medicine, Clinical Center, National Institute of Health, Bethesda, MD 20892, USA.
Bond
V P
VP
Sondhaus
C A
CA
Altman
K I
KI
D000222:Adaptation, Physiological / Q000528:radiation effects*; D019610:Cytoprotection; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals; D016014:Linear Models; D008452:Maximum Allowable Concentration; D015398:Signal Transduction / Q000528:radiation effects*
D005609:Free Radicals