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| Home > Publications database > Studying radiation generated DNA damage and how it is affected by oxygen and cellular metabolism |
| Dissertation / PhD Thesis | DKFZ-2021-02535 |
2021
Abstract: Cancer is one of the leading causes of death in the world and is routinely treated with radiotherapy. Radiation causes cellular damage by interacting either directly with DNA or indirectly via the formation of reactive oxygen species (ROS) resulting in double strand breaks (DSBs) and/or genomic instability. However, the efficacy of the radiation depends largely on the tumor microenvironment. Tumors tend to form hypoxic (low oxygen) regions due to their highly proliferative characteristics but are biologically programmed to adapt to these low oxygen situations via metabolic alterations to maintain their homeostasis. This can be problematic, however, as it can have a strong negative influence on the biological effects of ionizing radiation by increasing cellular radio-resistance and thereby reducing the therapy outcome (1,2).There are therefore two aims to this dissertation: 1. Analyse the indirect DNA damage of radiation on different non-small lung cancer cell lines (NSCLC) and correlate with nuclear and cytosolic radiation-induced ROS.2. Study how these adaptive responses to tumor hypoxia contribute to radio-resistance for a variety of different cancer cell lines and thus provide potential metabolic predictors to therapy outcome.
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