Induction of the Adaptive Response by X-rays is Dependent on Radiation Intensity

Abstract

Human lymphocytes pretreated with low (0.01 Gy) but not high (0.5 Gy) doses of X-rays become somewhat refractory to the induction of chromatid deletions by subsequent exposure to high (1.5 Gy) doses of X-rays (i.e. the yield of chromatid deletions is less than the sum of the yields induced by the pre-exposure and the subsequent challenge doses). This adaptive response can also be induced by pretreating the cells with very low, or even high, concentrations of tritiated thymidine. Because high concentrations of tritiated thymidine result in high doses of radiation that are delivered at very low dose-rates (i.e. <0.01 Gy/min), the lack of adaptation following high pre-treatment doses of X-rays could be attributed to their higher dose-rates. To test the effect of X-ray intensity on the induction of the adaptive response, lymphocytes were irradiated with 0.5 Gy of X-rays at 0.005-0.5 Gy/min at 28-30 h of culture, and then irradiated with 1.5 Gy at 48 h. Chromatid deletions were measured 6 h later. The results show that 0.5 Gy of X-rays given at low dose-rates (0.005 or 0.01 Gy/min), but not at high dose-rates (0.1, 0.2, or 0.5 Gy/min), are capable of inducing the adaptive response. Furthermore, experiments in which a male subject''s cells exposed to 0.5 Gy given at 0.005 Gy/min were cocultivated with a female subject''s cells irradiated with 0.5 Gy at 0.5 Gy/min showed that cell exposed to radiation at low and high intensity progress to metaphase equally and, therefore, that the lack of an adaptive response at high dose-rates cannot be attributed to selection of radioresistant cells. Although the induction of the adaptive response at higher X-ray doses occurs at low radiation intensity, there seems to be a minimum dose required for this effect, e.g., 0.01-Gy pretreatments induced the adaptive response when given at 0.2 Gy/min, but not at 0.005 Gy/min. Thus, the adaptive response is dependent both on the total dose of the pretreatment and on the rate at which the dose is given.