The effect of well-characterized, very low-dose x-ray radiation on fibroblasts

Abstract

The purpose of this study is to determine the effects of low-dose radiation on fibroblast cells irradiated by spectrally and dosimetrically well-characterized soft x-rays. To achieve this, a new cell culture x-ray irradiation system was designed. This system generates characteristic fluorescent x-rays to irradiate the cell culture with x-rays of well-defined energies and doses. 3T3 fibroblast cells were cultured in cups with Mylar ® surfaces and were irradiated for one hour with characteristic iron (Fe) K x-ray radiation at a dose rate of approximately 550 μGy/ hr. Cell proliferation, total protein analysis, flow cytometry, and cell staining were performed on fibroblast cells to determine the various effects caused by the radiation. Irradiated cells demonstrated increased proliferation and protein production compared to control samples. Flow cytometry revealed that a higher percentage of irradiated cells were in the G 0 /G 1 phase of the cell cycle compared to control counterparts, which is consistent with other lowdose studies. Cell staining results suggest that irradiated cells maintained normal cell functions after radiation exposure, as there were no qualitative differences between the images of the control and irradiated samples. The result of this study suggest that low-dose soft xray radiation might cause an initial pause, followed by a significant increase, in proliferation. An initial "pause" in cell proliferation could be a protective mechanism of the cells to minimize DNA damage caused by radiation exposure. The new cell irradiation system developed here allows for unprecedented control over the properties of the x-rays given to the cell cultures. This will allow for further studies on various cell types with known spectral distribution and carefully measured doses of radiation, which may help to elucidate the mechanisms behind varied cell responses to low-dose x-rays reported in the literature.

Inverse dose-rate effect of ionising radiation on residual 53BP1 foci in the eye lens

“…Our data indicate an inverse dose rate effect in the LEC for residual 53BP1 foci as a marker for DSBs, and it is hypothesised that this residual damage contributes to cataractogenesis. This study evidences the importance of determining the cell-specific effects of low dose and low dose-rate IR exposures on DNA repair in target tissues and show that the response can be cell and tissue specific due to for instance, competing processes such as cell proliferation and differentiation in a dose-rate dependant manner as observed in cell-based studies 63–65 .…”

First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells

“…However, the present data presented here of cell response to ionizing doses beyond 0.1 Gy does not fit into this model as cell damage is not increased in with LD irradiated cells and at the same time the proliferation is increased compared to shame irradiated cells. Those trends have also been recognized before in different non-carcinogen cell types [15,17,18,41] supporting the model of low-dose induced hormetic response. For example, in lung derived fibroblasts the exposure to radiation of 0.05 Gy stimulates the cell proliferation through transient activation of Raf (rapidly accelerated fibrosarcoma) and Akt (Protein kinase B) [41].…”

“…Rather, the data support the theory of low-dose induced hormetic responses in human cells describing beneficial low-dose effects of an agent that is harmful in high doses. Examples for such hormetic responses are the observed proliferation increasing effects of IR doses below 0.1 Gy in different non-carcinogen cell types [15,17,18,41].…”

“…As mentioned before, several studies have shown proliferation stimulating effects in different non-carcinogen cell types [15,17,18,41,42], but no data exist on those trends in ADSCs. Therefore, we also investigated the short-term effect of different radiation ranges in ADSCs.…”

“…However, further analysis of Jiang et al (2008) on much lower radiation doses revealed that radiation in the range below 0.1 Gy can act as growth-promoting stimuli in several normal human cell lines but not in leukemia and solid tumor cell lines in vitro and in vivo [15]. Liang et al (2016) and Truong et al (2018) confirmed those trends in fibroblasts and lung cancer cell lines later on [16,17]. Those findings lead to an important question for scientists in the field of regenerative medicine: Could we also induce the proliferation of mesenchymal stem cells by LD-RT below 0.1 Gy to enhance the success of several regenerative therapies?…”