Role of Different Enzymes in H₂O₂ Neutralization and Cellular Radioresistance Estimated by Mathematical Modeling

Reactive oxygen species (ROS) are fundamental components found in cells that exist in an oxygen environment. While they are often viewed as detrimental metabolic byproducts that can harm cells, leading to aging and cell death, they can also play a role in cellular regulatory processes and have beneficial effects. One of the main ROS present in all cells is hydrogen peroxide (H2O2), which can function as a signaling molecule in extra- and intracellular signaling. To enhance our understanding of how various enzymes regulate cellular H2O2 level we created a mathematical model of H2O2 neutralization and performed computer simulations to estimate the neutralization efficiency in various types of cells. Data on gene expression for genes participating in this process was incorporated into the calculations, along with enzymes’ regulation of oxidation and reduction processes. The conducted simulations demonstrate that cells originating from different tissues differently utilize systems neutralizing H2O2 which results in differences in H2O2 cellular levels. The simulation findings suggest that the differences in radiosensitivity seen in various cancer cell types may be linked to their effectiveness in neutralizing H2O2. Analysis of results from model simulations for colorectal, lung and breast cancer cell lines indicated that radiosensitive cell lines exhibit elevated levels of H2O2, attributed to the reduced efficiency of neutralizing enzymes.