Abstract
Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the uncertainty regarding the value of the dose rate effectiveness factor (DREF) used in radiological protection. While a LDR is defined as 0.1 mGy/min or lower, anything above that is seen as HDR. In cell and animal experiments, a dose rate around 1 Gy/min is usually used as representative for HDR. However, atomic bomb survivors, the reference cohort for radiological protection, were exposed to tens of Gy/min. The important question is whether gamma radiation delivered at very high dose rate (VHDR—several Gy/min) is more effective in inducing DNA damage than that delivered at HDR. The aim of this investigation was to compare the biological effectiveness of gamma radiation delivered at VHDR (8.25 Gy/min) with that of HDR (0.38 Gy/min or 0.79 Gy/min). Experiments were carried out with human peripheral mononuclear cells (PBMC) and the human osteosarcoma cell line U2OS. Endpoints related to DNA damage response were analysed. The results show that in PBMC, VHDR is more effective than HDR in inducing gene expression and micronuclei. In U2OS cells, the repair of 53BP1 foci was delayed after VHDR indicating a higher level of damage complexity, but no VHDR effect was observed at the level of micronuclei and clonogenic cell survival. We suggest that the DREF value may be underestimated when the biological effectiveness of HDR and LDR is compared.
Highlights
In the vast majority of countries worldwide, national systems of radiological protection are based on recommendations of the International Commission on Radiological Protection (ICRP)
Can risk factors derived from an acute exposure to high doses be used to predict health effects from chronic exposure to low doses? The ICRP assumes that this is not the case and recommends applying a dose and dose rate effectiveness factor (DDREF) of 2 for predicting cancer risks from low and chronic radiation exposures (ICRP 103 2007)
Different endpoints were analysed in two different cell types: micronuclei and mRNA levels of three known radiation-responsive genes FDXR, GADD45a and MDM2 were analysed in human peripheral blood lymphocytes and micronuclei, 53BP1 foci and clonogenic cell survival were analysed in the human osteosarcoma cell line U2OS which is stably transfected with a plasmid coding for the 53BP1 protein tagged with GFP (Bekker-Jensen et al 2005)
Summary
In the vast majority of countries worldwide, national systems of radiological protection are based on recommendations of the International Commission on Radiological Protection (ICRP) (https://www.icrp.org). The ICRP assumes that this is not the case and recommends applying a dose and dose rate effectiveness factor (DDREF) of 2 for predicting cancer risks from low and chronic radiation exposures (ICRP 103 2007). The criticism of DDREF is in part based on results of cell experiments which show that, per unit dose, the level of radiation-induced DNA mutations and stable-type chromosomal aberrations is the same after exposure to radiation at a high and low dose rate (Manesh et al 2014 and the papers within). An interesting and relevant question is whether radiation delivered at a dose rate higher than 1 Gy/min (referred to as very high dose rate) has a higher biological effectiveness than when delivered at a dose rate of 1 Gy/min If this is the case than experiments aiming at testing the validity of DDREF that were carried out at ca 1 Gy/min underestimate its value. Different endpoints were analysed in two different cell types: micronuclei and mRNA levels of three known radiation-responsive genes FDXR, GADD45a and MDM2 were analysed in human peripheral blood lymphocytes and micronuclei, 53BP1 foci and clonogenic cell survival were analysed in the human osteosarcoma cell line U2OS which is stably transfected with a plasmid coding for the 53BP1 protein tagged with GFP (green fluorescence protein) (Bekker-Jensen et al 2005)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
