Effects of Chronic LOw-dose Gamma Irradiation on GAstrointestinal Tumorigenesis

Ionising radiation has been linked to a number of cancer risks in humans, including gastrointestinal tumors. However information on low-dose and dose rate risks is lacking. This project uses a ApcMin/+ mouse model that is susceptible to the development of gastrointestinal tumors. In 2015, over 500 mice were chronically irradiated for two months to doses of 1 and 3 Gy at the FIGARO irradiation faciity at NMBU and then returned to Public Heath England to follow tumor development, as well as a variety of genotoxic and other endpoints. The risk factors from chronic irradiation will be compared to those for an similar dose given as acute radiation (data analysis ongoing). Results showed a dose dependent genotoxic response. response in mice. Biomarkers developed have also been tested in other organisms (zebrafish, c elegans).

This project is part of an application to the DoReMi internal call to consortium partners for integrated activities. The project addresses the collaborative projects accross WPs and the access to infrastructure part of the call. The project is a collabrat ion between three DoReMi consortium partners: NMBU/CERAD (University of Life Sciences, Centre of Excellence in Environmental Radioactivity), Public Health England (PHE, UK) and Folkehelse(NPHI, Norway). The proposal had been accepted by the DoReMi consort ium. The project application summary refers to NMBUs contribution to the Clogigat project. The aim of CLOGIGAT is to compare the quantitative effects of chronic low dose-rate (1.6 mGy h-1) and acute high dose-rate (3 Gy h-1) exposures to gamma radiatio n in the well characterised characterised ApcMin/+ mouse model of gastrointestinal tumorigenesis. The project will also give information on the genotoxicity of chronic vs. acute irradiation. The genotoxicity assessments will be done in blood, with transfe rability potential to humans following exposure to gamma irradiation. The project will increase the understanding of colon cancer development following chronic vs. acute gamma irradiation, and if the stage of the cancer development is correlated with geno toxic responses observed in blood samples. The profiling of the epigenetic regulatory miRNA in serum can potentially establish markers for both exposure and effects, also with transferability possibilities to humans. These studies will therefore contribut e to the evidence base for and inform the judgement on DDREF. In this respect, the proposed study is timely as ICRP has recently established a Task Group to examine the issue of risk inference at low doses and dose rates (Task Group 91). Overall, the pro ject will contribute towards an improved knowledge of low dose/dose rate radiation cancer risk, which is a key aim of DoReMi WP5, and is in line with key reaearch areas in the EC EURATOM programme.