Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIMEL. BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and –independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy.

Since 1957, broad proton beam radiotherapy with a spread out Bragg peak has been used for cancer treatment. More recently, studies on the use of proton therapy in the treatment of non-small cell lung cancer (NSCLC) were performed and although the benefit of using protons for the treatment of NSCLC is recognized, more work is needed to gather additional data for the understanding of cell response. Human A549 cell survival was evaluated by colony forming assay 11 days after 10 keV/μm proton beam irradiation at 0.1 and 1 Gy/min. The residual energy of the proton beam at the location of the irradiated cells was 3.9 MeV. In parallel, early effects on the cell viability and DNA damage were assessed and DNA synthesis was measured. The survival curve obtained was fitted with both the linear and the induced-repair models, as a hyper-radiosensitivity was evidenced at very low doses. Above 0.5 Gy, a linear shape was observed with the α parameter equal to 0.824 ± 0.029 Gy(-1). In addition, early cell death and cell proliferation arrest were enhanced. Moreover, a clear correlation between DNA damage and surviving fraction was observed. Finally, comparisons with X ray results indicate that proton irradiation at 10 keV/μm enhanced the tumor radiosensitivity with a significant dose-dependent decrease in the survival fraction. The RBE value of 1.9 ± 0.4 obtained for a 10% survival support this observation.

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It is believed that irradiation interacts with biological tissues to break or modify the DNA, which is the molecule contained in the nuclei of cells that carries all the relevant information for the organism. As such, radiation is dangerous for individuals; however, its properties can also be used in medicine, e. g. in cancer treatments. Nevertheless, the exact mechanisms of cellular response to radiation are not fully understood yet, especially for low doses (below 50 cGy), where non-targeted effects, i. e. that do not involve only the interactions radiation-DNA, are taking place. In order to deepen the knowledge of those non-targeted effects, a computer model of a population of cells irradiated in vitro was written, taking into account the phenomena in the low dose domain.As a start, two non-targeted effects were studied, the bystander effect and the low dose hyperradiosensitivity. The program was written in C++ and the technique of the cellular automaton was used. The clonogenic assay was reproduced; cells were seeded in a dish and if the colony they formed after a given period of time was bigger than 50 cells, the seeded cells were assumed to have survived. The direct effect of radiation was calculated by the traditional linear quadratic model and in addition cells were subjected to the bystander effect.Some simulations were run in the case of two cell lines, the hamster cell line V79 and the glioma cell line T98G. The results show that the bystander effect is unlikely to be limited to one period of the cell cycle, but that the low dose hyper-radiosensitivity and the bystander effect could be the same phenomenon. This work also suggests that the bystander effect may be significant after low doses of conventional radiotherapy. Such a model represents a very useful tool for solving problems that at the moment cannot be investigated experimentally.