Adaptive response and human benefit: Part I. A microdosimetry dose-dependent model

Abstract

The microdosimetry model allows concise determinations of specific energy hits within the cell critical nucleus volume to activate both protective and damage mechanisms. One or two low LET hits can result in reduction of both zero dose natural spontaneous and radiation-induced, carcinogenic causing damage. The model should be useful in comparing in vitro and in vivo broad beam to single track microbeam exposure data. The model is capable of determining, to an accuracy of +/- one specific energy hit, the minimum threshold for induction of radioprotective mechanisms--crucial to assessing the potential human benefit of adaptive response and other negative dose response behavior.

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

“…Recently a "reverse" adaptive response has been observed where the challenge dose is administered first, still showing an AR reduction after a later priming dose (Day et al 2007). Very low priming doses of radiation have also been shown to reduce natural, spontaneous occurring carcinogenic causing chromosome mutations in vitro (see Figures 2A-2C, Leonard 2007a) and in vivo (see Figure 3, Leonard 2007a). Thus, the potential benefit of adaptive response to human health risks is significant in the possible reduction in naturally occurring carcinogenic diseases.…”

“…Apoptosis is further suspected to be a radio-protective cellular action. There is conclusive evidence for some cells that radio-protection induction from adaptive response may be activated by a few or single charged particle track traversals (Leonard 2005(Leonard , 2007a(Leonard , 2007b through the sensitive region of individual cells, which in the prior work has been assumed to be the cell nucleus. Adaptive response (AR) occurs when with an initial priming dose, after a delay period on the order of 4-6 hours, a second higher challenge dose exhibits a reduced dose response as compared to the dose response without the initial priming dose, thus a delayed reduced dose response.…”

“…above about 40 mRem (0.04 cSv) per treatment nominally received by diagnostic x-ray, mammography, CAT and PET scan patients (Hall 2000). The recent works (Leonard 2005(Leonard , 2007a(Leonard , 2007b provide the only biophysical and/or a biochemical model presently available for application to AR experimental data to evaluate the above uncertainties.…”

Evidence for Radiation Hormesis after In Vitro Exposure of Human Lymphocytes to Low Doses of Ionizing Radiation

“…This is the approach we used to obtain results presented in Table 2 with 250-kVp X rays being used as reference. Leonard (2007) reported the value <z 1 > = 2 mGy/hit for 250-kVp X irradiation of human lymphocytes based on data from PohlRüling et al (Pohl-Ruling et al 1983). Values of LET used in scaling were obtained from NCRP Report 104 (NCRP 1990).…”

“…The indicated average hit depends on the volume of the biological micromasses considered (here all volumes in the irradiated target are the size of the cell nucleus). When estimated for a given radiation source and biological micromass, <z 1 > can then be scaled by LET (Leonard, 2007) or by values obtained for 1 μm size spherical biological micromasses as are reported in the BEIR IV Report (NAS/NRC 1988). This is the approach we used to obtain results presented in Table 2 with 250-kVp X rays being used as reference.…”