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. less than 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 cells 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.

A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

“…Dose rate, as well as dose, is relevant to potential human benefit from AR protection. Until recently only the works of Shadley and Wiencke (1989), cited above for human lymphocytes, had provided dose rate dependent AR response data, in their case involving challenge doses (1.5 Gy). We subsequently modified the microdosimetry model (Leonard 2007b) to encompass both dose and dose rate dependent activation of AR with priming doses and analyzed this challenge dose data of Shadley and Wiencke (Leonard 2005(Leonard , 2007b again showing that a minimum of at most two specific energy hits to the nucleus is sufficient to active AR but conclusively showing also the additional requirement that they occur within an interval of 9 seconds or rate of 6.7 hits per minute (see Figure 2, Leonard 2007b).…”

“…The benefit from the challenge dose effect would only be for the relatively rare incidence of accidental, large radiation dose exposures for individuals that happened to previously received a sufficient priming dose. Many investigators have preferred to study in vitro AR effects from the large challenge doses since chromosome aberration levels produced for scoring purposes are much larger, and better accuracy can be achieved, than that obtained solely from the low spontaneous cell damage (Wiencke et al 1986, Wolff et al 1989, Shadley and Wiencke 1989, Broome et al 2002, Wang et al 2003, Iyer and Lehnert 2002, Day et al 2006. However, some investigators have measured the ability of cells to undergo AR protection (from only low-LET priming dose radiation) of only the natural spontaneous aberrations continually occurring in cells from endogenic toxic damage to chromosomes (Pohl-Ruling et al 1983, Azzam et al 1996, Redpath and Antoniono 1998, Redpath et al 2001, Ko et al 2004, Hooker et al 2004, Elmore et al 2006, Koana et al 2007.…”

The radiation dose-rate effect in two human neuroblastoma cell lines

“…For HX142 we have previously shown that the values differ by a factor of 2 (Peacock et al, 1988). If this difference is real, a possible explanation might be sought in terms of inducible repair (Friedberg, 1985;Shadley & Wiencke, 1989 (Peacock et al, 1988;Yang et al, 1990). This shows directly that for any given dose the recovery observed in a split-dose experiment is greatest in the more sensitive lines.…”

Smoking and Hormesis as Confounding Factors in Radiation Pulmonary Carcinogenesis

“…The LNT hypothesis is widely used for estimating cancer risk, even though it has not been validated by scientific study and is not consistent with radiobiological data (Calabrese and Baldwin 2000;Tubiana 2003;Aurengo et al 2005). Comparatively little thought has been given by the BEIR committees and the ICRP to hormesis associated with the radiation adaptive response and thresholds at low doses and low dose-rates (Feinendegen et al 1988;Shadley and Wiencke 1989;NRC 1999NRC , 2005ICRP 2004), yet the BEIR VII report and the ICRP continue to support the LNT hypothesis (ICRP 2004). Because the LNT hypothesis is very well established and because many strong radiation protection organizations are in place, scientists and government officials are very reluctant to seriously consider the implications of the radiation hormesis phenomenon, which has obvious important health implications (Chen et al 2004).…”