Evaluation of the late genotoxic effect of flash radiation therapy in mouse tissue
The carcinogenic effect of radiation exposure and risk of development of secondary malignancies is well documented in patients receiving radiation therapy as part of their cancer treatment. FLASH radiation therapy has surfaced as a potential novel modality for administering radiation therapy. Whilst this way of administering radiation therapy has been shown to induce fewer acute side effects in experimental animals, the genotoxic effect of FLASH therapy has not been investigated. In this project we have sequenced exposed and unexposed tissues from mice 1 year after they have been treated with either FLASH or conventional electron radiation therapy. We will be investigating the level of radiation induced mutations in the tissues by performing a tumor normal analysis comparing unexposed(normal) versus exposed (tumor). We will use custom setting to allow for detection of mutations supported by only a few reads. As a control to assure that we are not detecting false signals we perform the same analysis using the unexposed tissue as tumor and the exposed as the normal. We will further evaluate the mutational signature to see that these overlap with the spectre expected for ionising radiation. This is a pilot project where we include tissues pairs from 4 mice. Each tissue is sequenced at a depth of 100X. If the methods indicated that these methods work and can reliable estimate the late genotoxic damage by radiation therapy our dataset will be expanded to include additional mice. The findings from this project is of great importance as the late carcinogenic effect from radiation therapy is seldomly accounted for in humans until many years after a therapeutic protocol has been in use.