EXPERIMENTAL AND MODELING APPROACHES TO STUDY THE EFFECT OF IRRADIATION ON CELL POPULATIONS

Abstract

In recent years, exceptional development is made towards a better understanding of proposed hallmarks of cancer treatment. However, with its high incidence, in the 21st century, it is still a challenge to find the optimum technique to treat cancer. Despite the different treatment modalities such as surgery, chemotherapy, radiation therapy, immunotherapy, and hormonal therapy, radiation therapy remains an essential component of tumor treatment; the main goal of tumor radiotherapy is to control and inhibit the proliferation of a malignant tumor cell. Even though a well-known feature of cancer cells promotes processes such as aggressiveness, metastasis, and invasiveness that have been associated with a worse clinical prognosis, this feature is the acidosis of the tumor microenvironment. Acidification of the tumor microenvironment comes due to the high glycolytic activity in cancer cells leading to extensive lactate production. Depending on the knowledge of cancer biology and radiation physics, the principles, methodologies, and techniques used to study the effect of ionizing radiations and the pH (intra and extracellular) on the cell growth of the F98 glioma cell line are discussed in this context. The first part of the thesis was the experimental part. The first section of the experimental part was to study the extracellular pH (pHe) as a therapeutic target to optimize the efficacy of radiotherapy, as this section focused on studying the cell growth and cell viability after placing the cell under different pH solutions and using different doses of radiation, the results in this part have hypothesized that changing the pHe will result in predictable changes in the radiation efficiency, which gives an argument for considering pH as a therapeutic target for future research based on the summation of radiotherapy with pH-regulating agents. The second section measured the intracellular pH (pHi) of the glioma F98-cell line. The results of this experiment gives an argument for considering the changes in pHi due to the radiation as a new biological effect of radiation on the cancer cell, these results were very interesting, but still, they need to be approved. The second part of the study was computational modeling or simulation, where in this work, a model was built to describe the cell growth of our cell line. The simulation results were able to give the same experimental data trend. Regardless the fact that the simulation can be developed to add more variables to give more information about the system.