Contribution to the clinical and laboratory study of tissue reactions observed radiosensitivity after radiotherapy of prostate cancer: potential radioprotective effect of statins

The tissue response of patients undergoing radiotherapy, despite identical treatment protocols, could have important variations. One of the questions asked to the radiobiology is to explain these variations (a posteriori approach) and if possible to predict it (a priori approach). The response of an organism and complex tissues to radiotherapy is the result of many determinants. Some belong to the tissue dynamics and homeostasis (inflammation, cytokines, etc.) and others to the sensitivity and cellular response (intrinsic sensitivity, DNA repair, regulation of cell death, etc.). About cellular determinants, our research team proposed to classify humans into three groups of different radiosensitivity levels, the first considered as normal is by far the largest (almost 75% of individuals), group II of intermediate radiosensitivity represents the majority of individuals having an abnormal response to radiotherapy. Group III gathers extremely rare conditions associated with marked or very marked hyper-radiosensitivity which are usually life threatening. Therefore patients in group II show either unexpected therapeutic response or severe radiation early or late side effects after doses for which normal tolerance is expected. Patients in group II can also be characterized by a strong predisposition to cancer and radiation-induced tumors. There is an inherent variability related to endogenous factors, such as the quality of DNA repair, or the spontaneous production of micronuclei; and exogenous factors. In this regard, certain medications may alter the cellular response to radiation therapy, such as statins, antiplatelet agents or anticoagulants. A posteriori approach: a single-center clinical study of 68 patients with prostate cancer treated by the same radiation oncologist in the same conditions, the frequency and severity of rectal side effects are compared to the use or not of statins: a radioprotective effect of statins toward radiation proctitis cannot be excluded. A priori approach: by studying the cellular and molecular radiation response in human fibroblasts (especially from healthy bowel tissue). Were studied: signaling and repair of DNA double-strand breaks by analysis of nuclear foci of MRE11; H2AX and pATM; radiation induced ATM protein transit from the cytoplasm to the nucleus was observed for the first time in rectal tissue fibroblasts. Statins appear to speed up this transit, making possible a radioprotective effect. These results open perspectives for further studies for the use of medications readily available that can modulate the severity of side effects of radiotherapy. (author)