Mechanisms of Injury to Normal Tissue after Radiotherapy

Abstract

Background The benefits of radiotherapy (RT) for cancer have been well documented for many years. However, even with targeted radiation delivery, many patients treated with radiation develop adverse effects. The purpose of this review was to analyze the current research into the biological basis of RT-induced normal tissue damage. Methods The PubMed and EMBASE databases were reviewed for articles on adverse effects of RT on normal tissue published from January 2005 through May 2012. Subsequently, abstracts of these articles were reviewed to identify articles with information relevant to the biological basis of RT-induced DNA damage and DNA repair. In addition, reference lists of the articles identified by the database search were reviewed, and referenced articles that seemed relevant were reviewed with no limitations on publication date. Results The database searches yielded 1751 publications. Of these, 1729 were eliminated because they did not address fundamental biology or were duplicates. A total of 22 articles were included. These articles revealed that many adverse effects are driven by chronic oxidative stress that affects the nuclear function of DNA repair mechanisms. Among normal cells undergoing replication, cells in S phase are most radioresistant because of overexpression of DNA repair enzymes, while cells in M phase are especially radiosensitive. Cancer cells exhibit increased radiosensitivity due to a breakdown in cell cycle checkpoints and repair mechanisms, and this increased radiosensitivity leads to accumulation of irreparable DNA lesions and cell death. Irradiated cells have an indirect effect on the cell cycle and survival of co-cultured non-irradiated cells. Method of irradiation and linear energy transfer to cancer cells versus bystander cells is shown to have an effect on cell survival, both cancerous and healthy. Conclusions RT-induced increases in reactive oxygen species in irradiated cells may signal healthy cells by increasing metabolic stress and creating DNA lesions. While normal cells express a strong ability to repair RT-induced DNA lesions, the side effects of RT and bystander cell signaling may have a larger impact than previously acknowledged.

Pain in cancer survivors

“…Second, ionising radiation directly damages DNA and the regulatory proteins which facilitate DNA repair. 86 The underlying treatment principle is that the DNA repair capacity of healthy cells is generally greater than that of cancerous cells, and that cancer cells proliferate more rapidly than most normal cells. Damage to DNA results in death of the affected cell through apoptosis or cell senescence.…”

Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients

“…Radiotherapy-induced DNA damage mainly consists of strand breaks and base alterations; therefore, the repair pathways involved in DNA damage are DNA double-strand break repair (DSBR) and base excision repair (BER) (25). The genetic variants of DNA repair-related genes may affect the capacity of the DNA repair pathways.…”

“…DNA BER is the major repair pathway of DNA single-strand breaks, including the apurinic/apyrimidinic (AP) site break and DNA base injury caused by radiation (25). The main enzymes involved in this pathway are DNA glycosylase, AP endonuclease, DNA polymerase and DNA ligase.…”

Introduction and Basic Concepts of Cancer

“…In this treatment method, a high dose of radiation, approximately 10 Gy for each fraction, is delivered with high precision and accuracy, lowering the amount of radiation absorbed by the neighboring normal cells (Choi and Cho, 2016). However, radiation therapies have many drawbacks including severe damage to adjacent neighboring tissues, thus overweighing its pros (Hubenak et al, 2014). For patients with metastatic spread or advanced stage disease, chemotherapy is the principal treatment regimen (Corrie, 2008).…”