Characterization of the Adaptive Response to Ionizing Radiation Induced by Low Doses of X Rays to Human Lymphocytes

Abstract

In previous studies we have shown that low doses of radiation from incorporated tritiated thymidine can make human lymphocytes less susceptible to the genetic damage manifested as chromatid breakage induced by a subsequent high dose of X rays. We have also shown that this adaptive response to ionizing radiation can be induced by very low doses of X rays (0.01 Gy; i.e., 1 rad) delivered during S phase of the cell cycle. To see if a low dose of X rays could induce this response in cells at other phases of the cell cycle, human lymphocytes were irradiated with 0.01 or 0.05 Gy before stimulation by phytohemagglutinin (G0) or with 0.01 Gy at various times after stimulation (G1), followed by 1.5 Gy (150 rad) at G2 phase. Although G0 lymphocytes failed to exhibit an adaptive response, G1 cells irradiated as early as 4 h after stimulation did show the response. Experiments were also carried out to determine how long the adaptive response induced by 0.01 Gy could persist. A 0.01-Gy dose was delivered to lymphocytes in the first S phase, followed by 1.5 Gy in the same or subsequent cell cycles. Lymphocytes receiving a 1.5-Gy dose at 40, 48, or 66 h after stimulation exhibited an adaptive response, whereas those receiving a 1.5-Gy dose at 90 or 114 h did not. Duplicate cultures containing bromodeoxyuridine showed that at 40 h all the lymphocytes were in their first cell cycle after stimulation, at 48 h half of the lymphocytes were in their first cell cycle and half in their second, and at 66 h 80% of the lymphocytes were in their third cell cycle. Thus the adaptive response persists for at least three cell cycles after it is induced by 0.01 Gy of X rays. In other experiments, the time necessary for maximal expression of the adaptive response was determined by delivering 0.01 Gy at hourly intervals 1-6 h before the 1.5-Gy dose. While a 4-h interval was enough for expression of the adaptive response, shorter intervals were not.

Low-Dose Gamma Irradiation Enhances Superoxide Anion Production by Nonirradiated Cells Through TGF-β1-Dependent Bystander Signaling

“…This theory has been reported in numerous studies in an ''adaptive response'' model. In this view, low doses of radiation primes the system, and when challenged by a large and acute dose of radiation the biological system performs better than a system that is given only the acute dose (154)(155)(156)(157).…”

Adaptive Response and Oxidative Stress

“…Since chromosomal damage was used as an endpoint in this study, it was once again assumed that an induction in DNA repair was responsible for this adaptation. It was subsequently demonstrated that the adaptive response was sustained through three cell cycles following the low dose exposure, after which the cells again became sensitive to high dose irradiation (14). Additional studies in human and rabbit lymphocytes indicated that these adaptive responses can be induced at all stages of the cell cycle with the questionable exeption of Go (15,16) and that, again, the adaptive response was sustained for three cell cycles.…”

Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates

“…Although the oxidative damage products 8-oxo G and TG are radiotoxic (61) and premutagenic lesions (56,60,62), they also can activate DNA repair (49,63,64), which is part of the general phenomenon of the adaptive response to both ionizing radiation and oxidative stress of different types (63)(64)(65)(66)(67)(68)(69)(70)(71). Adapted cells exhibit higher survival (survival adaptive response) and lower frequencies of chromosomal aberrations and gene mutations than do nonadapted cells, upon subsequent exposure to a challenging high dose of ionizing radiation (65)(66)(67)(68)(69)(70)(71). The adapting (priming) dose is usually at a level of one or several cGy and͞or is delivered at a low DR, e.g., 1 cGy͞min.…”

“…The adapting (priming) dose is usually at a level of one or several cGy and͞or is delivered at a low DR, e.g., 1 cGy͞min. There is evidence for the dependence of an adaptive response on DR with an optimal response of somatic cells, at some (but not all) conditions (69,71), near 1 cGy͞min, i.e., at a minimum value of mutation rate. This minimum could be a mutational signature of the antimutagenic radioadaptive response, as supported by studies of factors that can inhibit both radioadaptation and mutational DREs (e.g., ref.…”